Spa therapy and peripheral serotonin and dopamine function: a systematic review.

Spa therapy consists of multiple techniques based on the healing effects of water, including hydrotherapy, balneotherapy, and mud therapy, often combined with therapeutic exercises, massage, or physical therapy. Balneotherapy is a clinically effective complementary approach in the treatment of low-grade inflammation- and stress-related pathologies, especially rheumatic conditions due to its anti-inflammatory properties. The main objective of this investigation was to conduct a systematic review analyzing the available evidence on the effect of spa therapy on serotonin and dopamine function. The databases PubMed, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) were used from June to July 2023. Exclusion criteria were (1) articles not written in English, (2) full text not available, (3) article not related to the objective of the review. JADAD scale was used for methodological quality evaluation. Four studies were included in the systematic review. Two studies were related to serotonin in healthy individuals, one to serotonin in fibromyalgia, and one to dopamine in healthy individuals. One of the studies evaluated hydrotherapy, another one balneotherapy and mud-bath therapy, and the other two assessed balneotherapy interventions. Studies were very heterogeneous, and their methodological quality was low, making it difficult to draw clear conclusions regarding the effect of spa therapy on peripheral serotonin and dopamine function. The findings of this review highlight the lack of studies evaluating these neurotransmitters and hormones in the context of spa therapy. Further research is needed to evaluate the potential effects of these therapies on serotonin or dopamine function.

Gender and Age Differences in the Suppressive Effect of a 50 Hz Electric Field on the Immobilization-Induced Increase of Plasma Glucocorticoid in Mice.

We developed an experimental system to characterize the suppressive effect of extremely low-frequency (ELF) electric fields (EFs) on the stress response. We assessed differences in the EF effects by age and gender. Control, EF-alone, immobilization-alone, and co-treated groups were subjected to an EF (50 Hz, 10 kV/m). Co-treated mice were exposed to the EF for 60 min, with immobilization during the latter half. Our results indicate that the suppressive effects of ELF EFs on the stress response in immobilized mice occur regardless of gender or age. As stress plays an important role in the onset and progression of various diseases, these findings may have broad implications for understanding the efficacy of EFs in animal, and perhaps human, health. Bioelectromagnetics. 2020;41:156-163. © 2019 Bioelectromagnetics Society.

Response to adrenocorticotropic hormone or corticotrophin-releasing hormone and vasopressin in lactating cows fed an immunomodulatory supplement under thermoneutral or acute heat stress conditions.

Adrenal responsiveness was tested in nonpregnant, lactating Holstein dairy cows fed diets supplemented with OmniGen-AF (OG; Phibro Animal Health Corp., Teaneck, NJ), an immune modulator, and in nonsupplemented control (CON) cows following bolus infusions of a combination of corticotropin-releasing hormone (CRH; 0.3 µg/kg of BW) and arginine vasopressin (VP; 1.0 µg/kg of BW) or ACTH (0.1 IU/kg of BW) in 2 environments: thermoneutral [TN; temperature-humidity index (THI) <60] for 24 h/d and heat stress (HS; THI >68 for 17 h/d). Cows (506) were initially fed OG (n = 254) or CON (n = 252) diets for 44 d before selection of a subgroup of cows (n = 12; 6 OG, 6 CON) for the study. The 2 subgroups were balanced for parity, milk yield, and days in milk. All cows were transported to and housed in 2 environmentally controlled rooms at the University of Arizona Agricultural Research Complex (Tucson). Cows were given 3 d to acclimate to the rooms and then underwent 12 d of TN conditions and then 8 d of HS conditions for a total of 24 d on experiment. Cows were infused with CRH-VP on d 9 of TN and on d 1 of HS and with ACTH on d 10 of TN and on d 2 of HS. Hormone infusions took place at 1000 h (0 h) on each infusion day. Blood samples, taken in 30-min intervals, were first collected at 0800 h (-2 h) and were drawn until 1800 h (8 h). Before infusion, serum progesterone was elevated in OG cows compared with CON cows. Infusion of releasing factors (CRH-VP or ACTH) caused increases in serum cortisol and progesterone, but cortisol release was greater in CON cows than in OG cows during HS, whereas progesterone did not differ between the 2 treatments. Serum ACTH increased following infusion of releasing factors, but this increase was greater following CRH-VP infusion than ACTH infusion. Serum bovine corticosteroid-binding globulin also increased following infusion of releasing factors in both treatment groups, but this increase was greater during HS in cows fed OG. The free cortisol index (FCI) increased following CRH-VP and ACTH and was higher in HS than in TN for both OG and CON cows. However, the FCI response was blunted in OG cows compared with CON cows during HS. Heat stress enhanced the adrenal response to releasing factors. Additionally, the adrenal cortisol and FCI response to releasing factors was reduced during acute heat stress in cows fed OG. Collectively, these data suggest that OG supplementation reduced the adrenal responsiveness to factors regulating cortisol secretion during acute HS.

Fish pituitary show an active immune response after in vitro stimulation with Vibrio bacterin.

The pituitary is a central organ of the neuro-endocrine system in fish that plays critical roles in various physiological processes, including stress response and behavior. Although it is known that pituitary hormones can have a direct or indirect influence stimulating or suppressing the immune responses, whether there is a local immune response in the pituitary or what is the effect of the immune stimulus on the pituitary function in fish is unknown. With the aim to understand the interaction between the immune responses and the endocrine axes at the pituitary level, particularly the Hypothalamus-Pituitary-Interrenal (HPI) axis, pituitaries of rainbow trout (Oncorhynchus mykiss) were cultured in vitro, incubated with bacterin, or bacterin plus CRH, cortisol, human recombinant IL1ß, or spleen medium for 3 h, and then genes involved in pro-inflammation (il1ß, il8, tnfα1, ifnγ), anti-inflammation (tgfß1b, il10), immune modulation (mhcIIa, c3, mif) and stress response (crhbp, pomca, pomcb, gr1) were tested. Data showed that, incubation with bacterin alone and bacterin plus recombinant IL1ß or CRH, as well as medium from bacterin treated spleen caused significant up-regulation of pro-inflammatory genes il1ß and il8, while down-regulated the anti-inflammatory gene tgfß1b. Besides, recombinant IL1ß plus bacterin or alone caused raise of mhcIIa and tnfa, respectively. On the contrary, just a slight or even no alteration was recorded in the expression of stress response genes including crhbp, pomca, pomcb and gr1 in the in vitro cultured trout pituitary following this stimulation. These results suggest a local immune gene equipment in the pituitary of fish, and the potential for fish pituitary to develop both innate and adaptive immune responses, whereas that immune stimulation was not able to evoke a significant endocrine stress response in vitro.

Characterization of the suppressive effects of extremely-low-frequency electric fields on a stress-induced increase in the plasma glucocorticoid level in mice.

We recently suggested that an increase in the plasma glucocorticoid (GC) level in immobilized mice is suppressed by a 50-Hz electric field (EF) in an EF strength-dependent manner. The present study aimed to assess the anti-stress effect of EFs in three scenarios: exposure to an EF of either 50 or 60 Hz, which are the standard power frequencies in most regions; varying levels of environmental brightness during EF exposure; complete or partial shielding of the mouse from the EF. We compared the GC levels and blood parameters among control, EF-alone, immobilization-alone, and co-treatment groups. There was no difference between EFs of 50 and 60 Hz in terms of the suppression of the immobilization-induced increase in GC, that is, the anti-stress effect upon EF exposure. Examination of the effects of three environmental illuminance levels, 0, 200, and 490 lux, revealed that the effect of the EF was influenced by environmental illuminance. Shielding of the mice from the EF by wrapping the animals with an electrically conductive sheet inhibited the EF effect, which showed a negative correlation with the area shielded. Hence, environmental illuminance and the body area exposed to the EF might influence the effects of an EF on stress-induced increases in plasma GC levels in mice. Because stress plays an important role in the onset and progression of various diseases, these findings may have broad implications for understanding the efficacy of EFs in health. Bioelectromagnetics. 39:516-528, 2018 © 2018 Wiley Periodicals, Inc.

Mechanisms underlying the control of responses to predator odours in aquatic prey.

In aquatic systems, chemical cues are a major source of information through which animals are able to assess the current state of their environment to gain information about local predation risk. Prey use chemicals released by predators (including cues from a predator's diet) and other prey (such as alarm cues and disturbance cues) to mediate a range of behavioural, morphological and life-history antipredator defences. Despite the wealth of knowledge on the ecology of antipredator defences, we know surprisingly little about the physiological mechanisms that control the expression of these defensive traits. Here, we summarise the current literature on the mechanisms known to specifically mediate responses to predator odours, including dietary cues. Interestingly, these studies suggest that independent pathways may control predator-specific responses, highlighting the need for greater focus on predator-derived cues when looking at the mechanistic control of responses. Thus, we urge researchers to tease apart the effects of predator-specific cues (i.e. chemicals representing a predator's identity) from those of diet-mediated cues (i.e. chemicals released from a predator's diet), which are known to mediate different ecological endpoints. Finally, we suggest some key areas of research that would greatly benefit from a more mechanistic approach.

Juvenile hormone, but not nutrition or social cues, affects reproductive maturation in solitary alkali bees (Nomia melanderi).

Eusocial insect colonies are defined by extreme variation in reproductive activity among castes, but the ancestral conditions from which this variation arose are unknown. Investigating the factors that contribute to variation in reproductive physiology among solitary insects that are closely related to social species can help to fill this gap. We experimentally tested the role of nutrition, juvenile hormone (JH) and social cues on reproductive maturation in solitary alkali bees (Halictidae: Nomia melanderi). We found that alkali bee females emerge from overwintering with small Dufour's glands and small ovaries, containing oocytes in the early stages of development. Oocyte maturation occurs rapidly, and is staggered between the two ovaries. Lab-reared females reached reproductive maturity without access to mates or nesting opportunities, and many had resorbed oocytes. Initial activation of these reproductive structures does not depend on pollen consumption, though dietary protein or lipids may be necessary for long-term reproductive activity. JH is likely to be a limiting factor in alkali bee reproductive activation, as females treated with JH were more likely to develop mature oocytes and Dufour's glands. Unlike for related social bees, the effects of JH were not suppressed by the presence of older, reproductive females. These results provide valuable insight into the factors that influence reproductive activity in an important native pollinator, and those that may have been particularly influential in the evolution of reproductive castes.

Configuration-dependent variability of the effect of an electric field on the plasma glucocorticoid level in immobilized mice.

We recently reported that an immobilization stress-induced increase in glucocorticoid (GC) level was suppressed in mice exposed to an electric field (EF) of 50 Hz in a kV/m-dependent manner. In this study, we investigated the reproducibility of the suppressive effect induced by EF exposure by varying the voltage and distance between the electrodes (0.5 kV/50 mm, 1 kV/100 mm, 2 kV/200 mm) and comparing the effects on the plasma GC level. In addition, the effect of mice being in contact with the lower electrode or not was compared at 1 kV/100 mm. Immobilization-induced GC levels were significantly decreased in mice exposed to an EF at 1 kV/100 mm for 60 min (P < 0.01), but not in mice exposed to 0.5 kV/50 mm or 2 kV/200 mm. Furthermore, the suppressive effect of the 1 kV/100 mm EF was canceled when a polypropylene sheet (0.1 mm thick) was placed between the animal and lower electrode. Our findings corroborated that an EF of 10 kV/m inhibits stress-induced changes in the endocrine system in mice and demonstrated that this effect depends on the configuration of the EF exposure system, even when the EF strength remains the same. Bioelectromagnetics. 38:265-271, 2017. © 2017 Wiley Periodicals, Inc.

Time-dependent changes in the suppressive effect of electric field exposure on immobilization-induced plasma glucocorticoid increase in mice.

We recently reported that increased glucocorticoid (GC) levels in immobilized mice were suppressed by exposure to a 50-Hz electric field (EF) in kV/m-dependent and exposure duration-dependent manners. Here, we characterized time-dependent changes in the effect of EF exposure in immobilized mice. Using control, EF-alone, immobilization-alone, and co-treated groups, plasma GC levels, and blood properties were first measured (0-60 min) to observe changes induced by each treatment and measured again (60-120 min) to assess recovery from each treatment. The 50-Hz, 10-kV/m EF was formed in a parallel plate electrode. Co-treated mice were exposed to the EF for 60 min for the first measurement and were immobilized for the second half (30-60 min) of the EF exposure period. Plasma GC levels did not change significantly over time in the control and EF-alone groups. GC levels in the immobilization-alone and co-treated groups increased after immobilization, peaking 30 min after the start of immobilization and then decreasing gradually; however, the GC peak was lower in the co-treated group than in the immobilization-alone group (P < 0.05 at 50 and P < 0.001 at 60 min). Red blood cell counts, hemoglobin levels, and hematocrit values increased after immobilization but were not affected by the EF. Our findings indicate that the EF did not shift the peak of the time-dependent increase in plasma GC levels in immobilized mice but simply reduced it. Bioelectromagnetics. 38:272-279, 2017. © 2017 Wiley Periodicals, Inc.

Heightened stress response and cognitive impairment after repeated neonatal sevoflurane exposures might be linked to excessive GABAAR-mediated depolarization.

OBJECTIVE: Children with repeated exposures to anesthesia at an early age are at an increased risk of cognitive impairment. Data in the literature link increased developmental depolarizing γ-aminobutyric acid (GABA) type A receptor (GABAAR) at younger age to neurodevelopmental disorders. Here we investigated the involvement of GABAergic signaling during development in mediating the adverse effects of repeated sevoflurane exposures. METHODS: Sprague-Dawley male rats received repeated exposures to 3 % sevoflurane for 2 h daily for 3 consecutive days on postnatal days (P) 4, 5, and 6; maternally separated and unseparated rats served as controls. A subgroup of rats received three injections of the Na(+)-K(+)-2Cl(-) cotransporter inhibitor, bumetanide (1.82 mg/kg, intraperitoneally) 15 min prior to initiation of each sevoflurane exposure. RESULTS: The results showed that repeated neonatal sevoflurane exposures contribute to learning and memory impairment in the Morris water maze (MWM) at P60. The corticosterone level was significantly increased immediately after repeated neonatal sevoflurane exposures. Repeated neonatal sevoflurane exposures heightened the secretion of corticosterone in response to stress in P7 and P60 rats. Pretreatment of male rats prior to each sevoflurane exposure with bumetanide attenuated the corticosterone level immediately after repeated neonatal sevoflurane exposures, normalized endocrine response to stress at P7 and P60, and attenuated the sevoflurane-induced learning and memory impairment in the MWM. CONCLUSION: These data suggested that the heightened stress response and cognitive impairment after repeated neonatal sevoflurane exposures might be linked to excessive GABAAR-mediated depolarization.

Cognitive training prevents stress-induced working memory deficits.

BACKGROUND: Working memory is a fundamental cognitive process that is critically involved in planning, comprehension, reasoning, or problem-solving. Acute stress has been shown to impair working memory. This stress-induced working memory deficit has profound implications for our cognitive functioning in everyday life as well as for stress-related mental disorders. Here, we tested whether a cognitive training intervention can make working memory more resistant to disruptive effects of acute stress. METHODS: In a pre-registered, fully-crossed between-subjects design with the factors stress (vs. control) and cognitive training (vs. sham), one hundred twenty-three healthy men and women (aged 18-35 years) completed a daily cognitive training program targeting working memory-related processes or a sham training over a period of six weeks. After this six-week training intervention, participants underwent a standardized stress or control manipulation shortly before their working memory performance was tested. RESULTS: As expected, the exposure to acute stress led to a significant working memory impairment in the sham training group. Critically, although the subjective, autonomic, and endocrine stress responses were comparable in the two training groups, this stress-induced working memory impairment was abolished in the intervention training group. CONCLUSIONS: These results are the first to show that a cognitive training intervention directed at prefrontal and hippocampal functioning can prevent the detrimental effects of stressful events on working memory performance.

Acute and two-week effects of neotame, stevia rebaudioside M and sucrose-sweetened biscuits on postprandial appetite and endocrine response in adults with overweight/obesity-a randomised crossover trial from the SWEET consortium.

BACKGROUND: Sweeteners and sweetness enhancers (S&SE) are used to replace energy yielding sugars and maintain sweet taste in a wide range of products, but controversy exists about their effects on appetite and endocrine responses in reduced or no added sugar solid foods. The aim of the current study was to evaluate the acute (1 day) and repeated (two-week daily) ingestive effects of 2 S&SE vs. sucrose formulations of biscuit with fruit filling on appetite and endocrine responses in adults with overweight and obesity. METHODS: In a randomised crossover trial, 53 healthy adults (33 female, 20 male) with overweight/obesity in England and France consumed biscuits with fruit filling containing 1) sucrose, or reformulated with either 2) Stevia Rebaudioside M (StRebM) or 3) Neotame daily during three, two-week intervention periods with a two-week washout. The primary outcome was composite appetite score defined as [desire to eat + hunger + (100 - fullness) + prospective consumption]/4. FINDINGS: Each formulation elicited a similar reduction in appetite sensations (3-h postprandial net iAUC). Postprandial insulin (2-h iAUC) was lower after Neotame (95% CI (0.093, 0.166); p < 0.001; d = -0.71) and StRebM (95% CI (0.133, 0.205); p < 0.001; d = -1.01) compared to sucrose, and glucose was lower after StRebM (95% CI (0.023, 0.171); p < 0.05; d = -0.39) but not after Neotame (95% CI (-0.007, 0.145); p = 0.074; d = -0.25) compared to sucrose. There were no differences between S&SE or sucrose formulations on ghrelin, glucagon-like peptide 1 or pancreatic polypeptide iAUCs. No clinically meaningful differences between acute vs. two-weeks of daily consumption were found. INTERPRETATION: In conclusion, biscuits reformulated to replace sugar using StRebM or Neotame showed no differences in appetite or endocrine responses, acutely or after a two-week exposure, but can reduce postprandial insulin and glucose response in adults with overweight or obesity. FUNDING: The present study was funded by the Horizon 2020 program: Sweeteners and sweetness enhancers: Impact on health, obesity, safety and sustainability (acronym: SWEET, grant no: 774293).

Heat Stress: A Serious Disruptor of the Reproductive Physiology of Dairy Cows.

Global warming is a significant threat to the sustainability and profitability of the dairy sector, not only in tropical or subtropical regions but also in temperate zones where extreme summer temperatures have become a new and challenging reality. Prolonged exposure of dairy cows to high temperatures compromises animal welfare, increases morbidity, and suppresses fertility, resulting in devastating economic losses for farmers. To counteract the deleterious effects of heat stress, cattl e employ various adaptive thermoregulatory mechanisms including molecular, endocrine, physiological, and behavioral responses. These adaptations involve the immediate secretion of heat shock proteins and cortisol, followed by a complex network of disrupted secretion of metabolic and reproductive hormones such as prolactin, ghrelin, ovarian steroid, and pituitary gonadotrophins. While the strategic heat stress mitigation measures can restore milk production through modifications of the microclimate and nutritional interventions, the summer fertility records remain at low levels compared to those of the thermoneutral periods of the year. This is because sustainment of high fertility is a multifaceted process that requires appropriate energy balance, undisrupted mode of various hormones secretion to sustain the maturation and fertilizing competence of the oocyte, the normal development of the early embryo and unhampered maternal-embryo crosstalk. In this review, we summarize the major molecular and endocrine responses to elevated temperatures in dairy cows, as well as the impacts on maturing oocytes and early embryos, and discuss the consequences that heat stress brings about in dairy cattle fertility.

Which Patients Need Chemotherapy? From Pathological Risk Factors to Gene Signatures and Evaluation of Endocrine Response.

Background: Chemotherapy, used either before or after surgery, has significantly improved survival in early breast cancer. Accurate risk assessment is essential to avoid both overtreatment and undertreatment. This review provides an overview of the evolution of chemotherapy as well as risk factors for tailored systemic therapies in early breast cancer - from pathologic risk factors to gene expression signatures to endocrine response assessment. Summary: Chemotherapy has improved dramatically in recent decades from its beginnings with conventionally dosed cyclophosphamide plus methotexate plus 5-fluorouracil to dose-dense anthracycline- and taxane-containing regimens. Similarly, risk assessment has evolved starting from traditional pathologic risk factors such as tumor size, axillary nodal status, and grading. In recent decades, gene expression signatures have improved prognostic accuracy with a high level of evidence. In turn, these signatures can be further improved by incorporating the aforementioned pathologic factors. As an important step away from this static assessment, dynamic assessment of proliferation factor Ki-67 after short-term preoperative endocrine treatment has gained interest to improve risk assessment in early hormone receptor-positive breast cancer. Key Message: This review highlights advances in chemotherapy and risk assessment in early breast cancer, from pathologic risk factors for recurrence to gene expression signatures and endocrine response assessment. These developments are leading to better risk stratification and thus better adaptation of therapies.

Physiological (haematological, growth and endocrine) and biochemical biomarker responses in air-breathing catfish, Clarias batrachus under long-term Captan® pesticide exposures.

The sub-lethal toxicity of Captan® on selected haematological (Hemoglobin, Haematocrit, Mean Corpuscular Hemoglobin) growth (Condition factor, Hepatosomatic Index, Specific Growth Rate), biochemical (serum glucose, protein), and endocrine parameters (growth hormone, T3 and T4) in Clarias batrachus was examined under chronic exposures. Captan® was administered at predetermined exposure concentrations (0.53 and 1.06 mg/L) and monitored on days 15, 30, and 45 of the experimental periods. The experimental groups showed significantly lower values (p < 0.05) of haemoglobin content, hematocrit, MCH in Captan® exposed fish compared to control. Serum protein, k-factor and SGR were significantly lower in exposed fish. Endocrine responses (T3 and T4) emerged as the most sensitive biomarker category, depicting modulated responses between sub-chronic exposure at day-15 and chronic responses at day-45. In general, biomarker depictions indicate that Captan® exposures are capable of inducing stress-specific effects at the biochemical and physiological levels negatively impacting the overall health and longevity of such animals.

Suppression of Glucocorticoid Response in Stressed Mice Using 50 Hz Electric Field According to Immobilization Degree and Posture.

Various studies on immobilized BALB/c mice to evaluate changes in hormone levels associated with stress responses have advanced the characterization of multiple aspects of the biological actions of extremely low-frequency (ELF) electric fields (EFs). In this study, we aimed to investigate the effect of mouse posture on its stress responses and evaluate the importance of adjusting the stress degree in the model. Mice were immobilized inside centrifuge tubes and exposed to an ELF EF generated between parallel plate electrodes. Blood was collected under anesthesia immediately after EF exposure, and plasma glucocorticoids were assayed. The inhibitory effects of EFs on glucocorticoid elevation by immobilization were reproduced regardless whether mice were in the abdominal or lateral recumbent position, for the EF vector delivered to mice through the sagittal or frontal plane. The effect of ELF EF was reproduced in moderately and mildly stressed mice but not in severely immobilized mice. Hence, adjusting the stress degree is critical to the reproducibility of the results for this model. We characterized the effects of ELF EF on homeostasis, including the stress response, and provided valuable information for the scientific evaluation of the biological risks and medical applications of ELF EF.

Breast Cancer-Stromal Interactions: Adipose-Derived Stromal/Stem Cell Age and Cancer Subtype Mediated Remodeling.

Adipose tissue is characterized as an endocrine organ that acts as a source of hormones and paracrine factors. In diseases such as cancer, endocrine and paracrine signals from adipose tissue contribute to cancer progression. Young individuals with estrogen receptor-alpha positive (ER-α+) breast cancer (BC) have an increased resistance to endocrine therapies, suggesting that alternative estrogen signaling is activated within these cells. Despite this, the effects of stromal age on the endocrine response in BC are not well defined. To identify differences between young and aged ER-α+ breast tumors, RNA sequencing data were obtained from The Cancer Genome Atlas. Analysis revealed enrichment of matrix and paracrine factors in young (≤40 years old) patients compared to aged (≥65 years old) tumor samples. Adipose-derived stromal/stem cells (ASCs) from noncancerous lipoaspirate of young and aged donors were evaluated for alterations in matrix production and paracrine secreted factors to determine if the tumor stroma could alter estrogen signaling. Young and aged ASCs demonstrated comparable proliferation, differentiation, and matrix production, but exhibited differences in the expression levels of inflammatory cytokines (Interferon gamma, interleukin [IL]-8, IL-10, Tumor necrosis factor alpha, IL-2, and IL-6). Conditioned media (CM)-based experiments showed that young ASC donor age elevated endocrine response in ER-α+ BC cell lines. MCF-7 ER-α+ BC cell line treated with secreted factors from young ASCs had enhanced ER-α regulated genes (PGR and SDF-1) compared to MCF-7 cells treated with aged ASC CM. Western blot analysis demonstrated increased activation levels of p-ER ser-167 in the MCF-7 cell line treated with young ASC secreted factors. To determine if ER-α+ BC cells heightened the cytokine release in ASCs, ASCs were stimulated with MCF-7-derived CM. Results demonstrated no change in growth factors or cytokines when treated with the ER-α+ secretome. In contrast to ER-α+ CM, the ER-α negative MDA-MB-231 derived CM demonstrated increased stimulation of pro-inflammatory cytokines in ASCs. While there was no observed change in the release of selected paracrine factors, MCF-7 cells did induce matrix production and a pro-adipogenic lineage commitment. The adipogenesis was evident by increased collagen content through Sirius Red/Fast Green Collagen stain, lipid accumulation evident by Oil Red O stain, and significantly increased expression in PPARγ mRNA expression. The data from this study provide evidence suggesting more of a subtype-dependent than an age-dependent difference in stromal response to BC, suggesting that this signaling is not heightened by reciprocal signals from ER-α+ BC cell lines. These results are important in understanding the mechanisms of estrogen signaling and the dynamic and reciprocal nature of cancer cell-stromal cell crosstalk that can lead to tumor heterogeneity and variance in response to therapy.

Stress-Reducing Effect of a 50 Hz Electric Field in Mice after Repeated Immobilizations, Electric Field Shields, and Polarization of the Electrodes.

In BALB/c mice, immobilization-increased plasma glucocorticoid (GC) levels are suppressed by extremely low frequency (ELF) electric fields (EF). The aim of this study was to advance our understanding of the biological effects of ELF-EF, using its suppressive effect on the GC response. Mice were exposed to a 50 Hz EF of 10 kV/m via a parallel plate electrode and immobilized as needed. We examined the suppressive effect of ELF-EF on GC level change after repeated immobilizations, electrode polarization, and EF shielding of different portions of the mouse body parts. Additionally, bodyweight changes owing to stress and EF were examined. Immobilization-induced reduction in the plasma GC levels was reproduced in mice with stress and EF exposure, regardless of the stress episode numbers and electrode polarization. Furthermore, when the head of mice was shielded from the EF, the suppressive effect was possibly relatively lower than that when the abdomen was shielded. The bodyweight of the mice decreased for 3 days after immobilization before recovering; ELF-EF did not affect the bodyweight. Thus, to elicit the biological effects of the EF, not only the size of the area where the EF is distributed but also the area where the field is distributed should be important. The results also confirmed the stableness of the present experimental system, at least in terms of the stress-reducing effect. In addition, the restriction in this study caused weight loss, but ELF-EF was not considered to affect it. The results improve the understanding of the biological effect and medical applications of ELF-EF.

Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics.

Atypical antipsychotics (AAP) or second-generation antipsychotics are the clinical option for schizophrenia treatment during acute psychoses, but they are also indicated for maintenance during lifetime, even though they are being used for other psychiatric conditions in clinical practice such as affective disorders and autism spectrum disorder, among others. These drugs are differentiated from typical antipsychotics based on their clinical profile and are a better choice because they cause fewer side effects regarding extrapyramidal symptoms (EPS). Even though they provide clear therapeutic benefits, AAP induce peripheral effects that trigger phenotypic, functional, and systemic changes outside the Central Nervous System (CNS). Metabolic disease is frequently associated with AAP and significantly impacts the patient's quality of life. However, other peripheral changes of clinical relevance are present during AAP treatment, such as alterations in the immune and endocrine systems as well as the intestinal microbiome. These less studied alterations also have a significant impact in the patient's health status. This manuscript aims to revise the peripheral immunological, endocrine, and intestinal microbiome changes induced by AAP consumption recommended in the clinical guidelines for schizophrenia and other psychiatric disorders.

Differential Regulation and Targeting of Estrogen Receptor α Turnover in Invasive Lobular Breast Carcinoma.

Invasive lobular breast carcinoma (ILC) accounts for 10% to 15% of breast cancers diagnosed annually. Evidence suggests that some aspects of endocrine treatment response might differ between invasive ductal carcinoma (IDC) and ILC, and that patients with ILC have worse long-term survival. We analyzed The Cancer Genome Atlas dataset and observed lower levels of ESR1 mRNA (P = 0.002) and ERα protein (P = 0.038) in ER+ ILC (n = 137) compared to IDC (n = 554), and further confirmed the mRNA difference in a local UPMC cohort (ILC, n = 143; IDC, n = 877; P < 0.005). In both datasets, the correlation between ESR1 mRNA and ERα protein was weaker in ILC, suggesting differential post-transcriptional regulation of ERα. In vitro, 17ß-estradiol (E2) decreased the rate of degradation and increased the half-life of ERα in ILC cell lines, whereas the opposite was observed in IDC cell lines. Further, E2 failed to induce robust ubiquitination of ERα in ILC cells. To determine the potential clinical relevance of these findings, we evaluated the effect of 2 selective estrogen receptor downregulators (SERDs), ICI 182,780 and AZD9496, on ERα turnover and cell growth. While ICI 182,780 and AZD9496 showed similar effects in IDC cells, in ILC cell lines, AZD9496 was not as effective as ICI 182,780 in decreasing ERα stability and E2-induced proliferation. Furthermore, AZD9496 exhibited partial agonist activity in growth assays in ILC cell lines. Our study provides evidence for a distinct ERα regulation by SERDs in ILC cell lines, and therefore it is important to include ILC models into preclinical and clinical testing of novel SERDs.