Serum Adrenocorticotropic Hormone Levels Research Articles

Paeoniflorin Alleviates Anxiety and Visceral Hypersensitivity via HPA Axis and BDNF/TrkB/PLCγ1 Pathway in Maternal Separation-induced IBS-like Rats.

Irritable Bowel Syndrome (IBS) is a prevalent gastrointestinal disorder that significantly diminishes the quality of life for affected individuals. The pathophysiology of IBS remains poorly understood, and available therapeutic options for IBS are limited. The crucial roles of brain-gut interaction, which is mediated by the Hypothalamic-Pituitary-Adrenocortical (HPA) axis and the autonomic nervous system in IBS, have attracted increasing attention. The objective of this study was to examine the impact of paeoniflorin (PF) on anxiety and visceral hypersensitivity in maternal separation-induced IBS-like rats. The IBS-like rat model was established through the implementation of Maternal Separation (MS) and subsequently subjected to various doses of PF administered via oral gavage for 14 days. Anxiety-like behavior was evaluated using the Open Field Test (OFT) and Elevated Plus Maze (EPM) test. The assessment of visceral sensitivity involved the utilization of the Abdominal Withdrawal Reflex (AWR) score and electromyographic (EMG) responses of the external oblique muscle in response to colorectal distention. The levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), and corticotrophin-releasing hormone (CRH) were examined by ELISA. Quantitative real-time PCR (qRT-PCR) and immunofluorescence were employed to detect the expressions of CRH receptors 1 (CRHR1) and 2 (CRHR2). Glucocorticoid receptors (GR), mineralocorticoid receptor (MR), brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and phospholipase C γ1 (PLCγ1) were examined by Western blot. The results showed that MS induced anxiety-like behavior and visceral hypersensitivity, while PF treatment attenuated these changes. Furthermore, the HPA axis hyperactivity in MS rats was attenuated by PF treatment, indicated by reduced serum ACTH, CORT, and CRH levels and recovered hippocampal CRHR1 and GR expressions. In addition, PF inhibited BDNF/TrkB signaling by downregulating the protein levels of BDNF, TrkB, and phospho-PLCγ1 in the colon. These findings suggest that PF alleviated anxiety and visceral hypersensitivity in MS-induced IBS-like rats, which may be the modulation of HPA axis activity and BDNF/TrkB/PLCγ1 signaling pathway.

Clinical characteristics of programmed cell death-1 inhibitor-associated hypophysitis

Objective: To explore the clinical features of programmed cell death-1 (PD-1) inhibitor-associated hypophysitis and improve the understanding of the disease. Methods: For the present retrospective case series study, the clinical data of patients with PD-1 inhibitor-associated hypophysitis who were treated at the Affiliated Hospital of Hebei University and the 3rd Hospital of Hebei Medical University from January 2020 to May 2023 were collected for analysis of clinical manifestations and prognosis. Results: Fifteen cases of PD-1 inhibitor-induced hypophysitis were included, with 13 males and 2 females. The mean age of onset was (62.1±7.5) years, and the median time of onset was 6.5 (4.7, 11.6) cycles of PD-1 inhibitor. At diagnosis, 14 patients complained of gastrointestinal symptoms, and 12 patients complained of fatigue. There were 12, 1, 1, 5, and 1 cases of hyponatremia, hypokalemia, hypoglycemia, hypotension, and fever, respectively. Secondary adrenocortical insufficiency occurred in all cases. Moreover, four patients had secondary hypothyroidism, and two patients had secondary hypogonadism. Posterior pituitary hypofunction was not found. Pituitary MRI showed one case each of vacuolar sella turcica, pituitary cystic lesion, pituitary stalk slightly shifted to the left, high metabolism in the sella turcica, and pituitary abnormal signal, while no abnormalities were found in 11 cases. The follow-up time was (47.66±11.93) weeks. At the last follow-up, one patient's serum levels of adrenocorticotropic hormone and cortisol returned to normal. Conclusions: Hypophysitis associated with PD-1 inhibitors occurs later, and gastrointestinal symptoms and fatigue are the most common clinical manifestations. PD-1 inhibitor-associated hypophysitis mainly manifests as adrenocortical hypofunction, and some cases manifest as hypothyroidism and hypogonadism. In addition, patients with PD-1 inhibitor-associated hypophysitis show no obvious imaging changes in the pituitary gland.

Perfluorotetradecanoic acid exposure to adult male rats stimulates corticosterone biosynthesis but inhibits aldosterone production.

Perfluorotetradecanoic acid (PFTeDA) is a novel perfluoroalkyl substance that ubiquitously exists in the environment. However, whether PFTeDA affects adrenal cortex function remains unclear. Male Sprague-Dawley rats (age of 60 days) were daily administered with PFTeDA (0, 1, 5, and 10 mg/kg body weight) through gavage for 28 days. PFTeDA did not change body and adrenal gland weights. PFTeDA markedly elevated serum corticosterone level at 10 mg/kg but lowering serum aldosterone level at this dosage without influencing serum adrenocorticotropic hormone level. PFTeDA thickened zona fasciculata without affecting zona glomerulosa. PFTeDA remarkably upregulated the expression of corticosterone biosynthetic genes (Mc2r, Scarb1, Star, Cyp21, Cyp11b1, and Hsd11b1) and their proteins, whereas downregulating aldosterone biosynthetic enzyme Cyp11b2 and its protein, thereby distinctly altering their serum levels. PFTeDA markedly downregulated the expression of antioxidant genes (Sod1 and Sod2) and their proteins at 10 mg/kg. PFTeDA significantly decreased SIRT1/PGC1α and AMPK signaling while stimulating AKT1/mTOR signaling. Corticosterone significantly inhibited testosterone production by adult Leydig cells at >0.1 μM in vitro; however aldosterone significantly stimulated testosterone production at 0.1 nM. In conclusion, exposure to PFTeDA at male rat adulthood causes corticosterone excess and aldosterone deficiency via SIRT1/PGC1α, AMPK, and AKT1/mTOR signals, which in turn additively leads to testosterone deficiency.

Serum ACTH and Cortisol Level is Associated with the Acute Gastrointestinal Injury Grade in ICU Patients.

The relationship between acute gastrointestinal symptoms and cortisol or adrenocorticotropic hormone (ACTH) levels has rarely been reported. We hypothesized that the elevation of serum cortisol or ACTH levels may be correlated with the severity of the acute gastrointestinal injury grade (AGI). This study was an observational study. All patients were admitted to the ICU between 2019.1.1 and 2020.1.1.. Serum ACTH and cortisol levels and clinical data were collected from the electronic medication records. The highest AGI grade during the ICU stay was the major endpoint to observe. The patient was treated in a standard procedure in the ICU. A total of 235 patients were included in our study, 132 of whom developed AGI. In univariate regression, cortisol level was found to be a risk factor for 28-day mortality. Serum cortisol and ACTH levels correlated with APACHE II, AGI grade, PCT, and CRP levels. Spearman analysis and partial correlation analysis indicated that cortisol and ACTH levels were correlated with AGI grade. The ACTH and cortisol levels were positively correlated with the higher severity of AGI grade. The cortisol level may be a useful way to access the GI injury.

Serum Levels of Cortisol and Adrenocorticotropic Hormone and their Association with Depression in Environmentally Exposed Populations in Kazakhstan.

This study aimed to investigate the serum levels of cortisol and adrenocorticotropic hormone (ACTH) and the prevalence of depression in the environmentally exposed population of Kazakhstan compared to the environmentally unexposed populations. Additionally, the study aimed to evaluate the capacity of cortisol and ACTH to predict moderate and severe depression in populations exposed to environmental risk factors. This cross-sectional study included 1881 nominally healthy individuals aged between 18-52years who were lifelong residents of Abay, Borodulikha, Ust-Kamenogorsk, Aksay, and Berezovka settlements, which are characterized by exposure to various types of environmental pollutants. Comparisons were made with residents of control sites with no known industrial or radioactive pollution (Uralsk and Kurchum). The Russian version of the PHQ-9 questionnaire was used to evaluate the presence and severity of depression. Serum cortisol levels were measured using solid-phase chemiluminescent immunoassay, while serum ACTH levels were tested with chemiluminescent assays. Populations exposed to environmental pollution from condensate gas extraction (Berezovka and Aksay) had higher median serum cortisol concentrations. However, the populations of the two controls had the highest median serum levels of ACTH. The median total PHQ-9 scores were the lowest in residents of control sites, which also had the highest proportion of individuals with no or minimal depression. Both serum cortisol and ACTH identified moderate, moderately severe, and severe depression. The findings highlight the potential impact of environmental pollution on stress hormone levels and depression, calling for further research and public health interventions to address this issue.

Sargassum horneri Extract Attenuates Depressive-like Behaviors in Mice Treated with Stress Hormone.

Sargassum horneri, a brown seaweed, is known for its various health benefits; however, there are no reports on its effects on depression. This study aimed to investigate the antidepressant effects of S. horneri ethanol extract (SHE) in mice injected with corticosterone (CORT) and to elucidate the underlying molecular mechanisms. Behavioral tests were conducted, and corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and CORT levels were measured. A fluorometric monoamine oxidase (MAO) enzyme inhibition assay was performed. Neurotransmitters like serotonin, dopamine, and norepinephrine levels were determined. Moreover, the ERK-CREB-BDNF signaling pathway in the prefrontal cortex and hippocampus was evaluated. Behavioral tests revealed that SHE has antidepressant effects by reducing immobility time and increasing time spent in open arms. Serum CRH, ACTH, and CORT levels decreased in the mice treated with SHE, as did the glucocorticoid-receptor expression in their brain tissues. SHE inhibited MAO-A and MAO-B activities. In addition, SHE increased levels of neurotransmitters. Furthermore, SHE activated the ERK-CREB-BDNF pathway in the prefrontal cortex and hippocampus. These findings suggest that SHE has antidepressant effects in CORT-injected mice, via the regulation of the hypothalamic-pituitary-adrenal axis and monoaminergic pathway, and through activation of the ERK-CREB-BDNF signaling pathway. Thus, our study suggests that SHE may act as a natural antidepressant.

The Hormonal Status Comparison of Unilateral and Bilateral Adrenal Adenomas: Are They the Same?

Objective: It is not yet clear whether unilateral/bilateral adenomas are different in terms of both functionality and etiology. We investigated whether there were differences in hormonal profiles and evaluate the cortisol secretion profiles of unilateral and bilateral adenomas. Methods: Hormonal secretory profiles and clinical features of patients with adenomas were collected. Detailed evaluation was made in terms of hypercortisolemia. Results: Of the 184 patients examined, 140 had unilateral and 44 had bilateral adenomas. 73% of the patients were female and the mean body mass index was 34±8.1kg/m2. The mean age was 57.1±9.8 years. The average size of the adrenal masses was 23.3±10.5mm. While 83% of the evaluated adenomas were nonfunctional, ACS was found in 11% (n:20), hyperaldosteronism in 4% (n:8), and pheochromocytoma (PCC) in 2% (n:3) of the patients. The prevalence of ACS in bilateral/unilateral adenomas was 20.5%/7.9%, respectively. While serum adrenocorticotropic hormone level (25.6±16.6vs19.3±15µg/dL), urinary free cortisol level (162.3±108.3vs243.3±234.2µg/day), and low-dose-dexamethasone-suppression-test results (1.6±1.9vs1.73±1.7µg/dL) were not statistically different, the only difference between unilateral and bilateral adenomas was in serum DHEA-S level (141.4±85vs77.7±73.8 µg/dL, p:0.003). Conclusion: Although there is no significant difference between the two groups in terms of clinical findings, it is clear that ACS is more prevalent in bilateral adenomas than unilateral. Because of the negative effects of long-term hypercortisolism, precise management of ACS is noteworthy. The evaluation of ACS should be done more carefully in bilateral adenomas considering that ACS is more in bilateral adenomas than unilateral. According to our findings, we also suggest that DHEA-S may be an indicator for ACS.

Recurrent bilateral adrenal infarction with myelodysplastic/myeloproliferative neoplasm-unclassifiable (MDS/MPN-U): a case report

BackgroundBilateral adrenal infarction is rare and only a small number of cases have been reported so far. Adrenal infarction is usually caused by thrombophilia or a hypercoagulable state, such as antiphospholipid antibody syndrome, pregnancy, and coronavirus disease 2019. However, adrenal infarction with myelodysplastic/myeloproliferative neoplasm (MDS/MPN) has not been reported.Case presentationAn 81-year-old man with a sudden severe bilateral backache presented to our hospital. Contrast-enhanced computed tomography (CT) led to the diagnosis of bilateral adrenal infarction. Previously reported causes of adrenal infarction were all excluded and a diagnosis of MDS/MPN-unclassifiable (MDS/MPN-U) was reached, which was considered to be attributed to adrenal infarction. He developed a relapse of bilateral adrenal infarction, and aspirin administration was initiated. Partial primary adrenal insufficiency was suspected as the serum adrenocorticotropic hormone level was persistently high after the second bilateral adrenal infarction.ConclusionThis is the first case of bilateral adrenal infarction with MDS/MPN-U encountered. MDS/MPN has the clinical characteristics of MPN. It is reasonable to assume that MDS/MPN-U may have influenced bilateral adrenal infarction development, considering the absence of thrombosis history and a current comorbid hypercoagulable disease. This is also the first case of recurrent bilateral adrenal infarction. It is important to carefully investigate the underlying cause of adrenal infarction once adrenal infarction is diagnosed, as well as to assess adrenocortical function.

Loganin improves chronic unpredictable mild stress-induced depressive-like behaviors and neurochemical dysfunction.

Cornus officinalis Sieb. et Zucc., is a valuable herb commonly used in Chinese medicine clinics. Loganin is a major iridoid glycoside obtained from the traditional Chinese herb Corni Fructus. Loganin, which has been shown to improve depression-like behavior in mice exposed to acute stress, is probably a potential antidepressant candidate. Loganin was evaluated for its effect on chronic unpredictable mild stress (CUMS) induced depressive-like mice, and its action mechanisms were explored. ICR mice were subjected to the CUMS stimulation method to induce depression. The therapeutic effect of loganin on depressive-like behavior was evaluated by a series of behavioral tests such as sucrose preference test (SPT), forced swim test (FST), tail suspension test (TST) and open-field test (OFT). In addition, the serum levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were measured using ELISA. The levels of monoamine neurotransmitters were detected by high performance liquid chromatography-electrochemical detection (HPLC-ECD). The levels of brain-derived neurotrophic factor (BDNF) in the hippocampus were measured using western blot analysis. The results showed that CUMS induced depressive-like behaviors in mice, as indicated by behavioral tests. Administration of loganin increased the sucrose preference in SPT, as well as decreased the immobility time in FST and TST. Loganin could also improve food intake, and increased crossing times in the OFT. In mechanism, loganin restored the secretion of monoamine neurotransmitters, ACTH and CORT to normal levels. In addition, loganin elevated the expression of BDNF in the hippocampus. In conclusion, loganin exerts antidepressant-like effects in CUMS model mice through modulating monoamine neurotransmitters, ACTH, CORT and BDNF. Loganin effectively ameliorated depressive-like symptoms in CUMS-exposed mice by increasing 5-hydroxytryptamine (5-HT) and dopamine (DA) levels, alleviating hypothalamic-pituitary-adrenal (HPA) axis dysfunction, and increasing BDNF expression. In conclusion, the findings of the current study extensive evidence for the application of loganin in stress-associated disorders, specifically targeting depression.

Risk factors for testicular adrenal rest tumors in pediatric patients with congenital adrenal hyperplasia

Testicular adrenal rest tumors (TARTs) predominantly occur in patients with congenital adrenal hyperplasia (CAH) and may interfere with the function of the testicles. This study aimed to identify the factors that contribute to the occurrence of TARTs in patients with CAH and influence their volume. This was a comparative cross-sectional study. Male patients aged 0-16 years with CAH were included. Weight, height, bone age determination, biochemical and androgenic profiles, and testicular ultrasound were performed. Patients were divided into those with and without TARTs and the between-group differences were assessed using the Mann-Whitey U test and Fisher's exact test. A ROC curve was created for serum ACTH levels to identify the cut-off point to diagnose TARTs. Variables that influenced the volume of the TARTs were identified using Spearman's correlation coefficient. TARTs were observed in seven (19.4%) of 36 male children with CAH. Of the patients with TARTs, 85.7% were pubertal. Serum concentrations of adrenocorticotropic hormone (ACTH) levels were significantly higher in patients with TARTs than in those without (309.0pg/mL vs. 45.2pg/mL; p=0.006). ACTH levels >200pg/mL were found to predict the presence of TARTs (sensitivity 85.7%; specificity 86.2%) (Figure). The factors found to correlate with TARTs volume were ACTH levels (coefficient 0.004; p=0.009) and the three-year average of serum testosterone levels (coefficient 9.64; p=0.003).] DISCUSSION: The main limitation of this study was the small sample size. However, an ACTH cut-off point to predict insufficient hormonal treatment and consequently the presence of TART had not been described. High ACTH (>200pg/mL) was found to be predictive insufficient hormonal treatment in patients with CAH. The three-year average of serum testosterone levels and ACTH concentrations were correlated with the volume of TARTs.

The Association of the Hypothalamic-Pituitary-Adrenal Axis with Appetite Regulation in Children with Fetal Alcohol Spectrum Disorders (FASDs)

Prenatal alcohol exposure causes growth impairment and a wide range of developmental, physical, and cognitive disorders in children, collectively referred to as fetal alcohol spectrum disorders (FASDs). In the course of FASDs, abnormalities can also affect eating behavior and nutritional status, but these problems have received little attention. Therefore, the aim of our study was to determine the levels of hormones involved in the action of the hypothalamic-pituitary-adrenal axis: proopiomelanocortin (POMC), cortisol, and adrenocorticotropic hormone (ACTH), in the serum of patients with FASDs. To our knowledge, none of these hormones studied have yet been evaluated in FASDs to date. We investigated 62 FASD patients and 23 healthy controls by applying an enzyme-linked immunosorbent method (ELISA). Fasting POMC levels were significantly lower in patients with FASDs (10.97 vs. 18,57 ng/mL, p = 0.039) compared to controls. However, there were no differences in cortisol concentrations. Additionally, the sex and subgroup status (fetal alcohol syndrome (FAS), neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE), and FASD risk) did not affect hormone levels. POMC was positively correlated with some clinical parameters such as age, BMI percentile, carbohydrate biomarkers, and ACTH. A positive correlation was observed between ACTH and cortisol levels, as well as ACTH and cholesterol levels. Data analysis showed no HPA axis abnormalities in the form of elevated serum cortisol and ACTH levels. Differences in POMC concentration may indicate the involvement and/or impairment of central nervous system structures in hormonal alterations in FASD individuals, caused by prenatal alcohol exposure. Hormonal dysregulation in FASDs can contribute to reduced growth and development, as well as many other disturbed processes, including neurological/neurodevelopmental dysfunctions. Further insightful studies involving a larger group of patients are needed to determine the potential impact of the measured hormones.

Familial Glucocorticoid Deficiency Presenting with Tonic-Clonic Seizure: A Case Report

Familial glucocorticoid deficiency (FGD) is a rare cause of adrenal insufficiency in children. The condition can present with features of low cortisol and high adrenocorticotropic hormone (ACTH). Late diagnosis can be associated with high morbidity and high mortality rates. The presented case was a three-year-old Saudi girl who presented with dehydration and seizures as a complication of hypoglycemia. The initial examination and investigations revealed hyperpigmentation and normal arterial blood pressure. The lab investigation and genetic study revealed hypoglycemia, metabolic acidosis, low serum cortisol: 53 nmol/L (N: 140-690 nmol/L), normal androgens: 0.65 nmol/L (N: 0.5-2.4 nmol/L) and aldosterone: 50 pgmL (N: 2-200 pg/mol), and normal serum electrolytes. The ACTH level was more than 2000 pg/mL. A genetic study indicated a homozygous likely variant in the nicotinamide nucleotide transhydrogenase (NNT) gene, consistent with a genetic diagnosis of autosomal recessive glucocorticoid deficiency type 4. No mutations were found regarding MC2R, MRAP, and TXNRD2. The child was started on hydrocortisone, initially at 100 mg/m2/dose IV and then 100 mg/m2/day divided to q 6 hr. The dose was gradually decreased to 15 mg/m2/day PO BID, with clinical improvement and normalization of the serum ACTH level. The autosomal recessive glucocorticoid deficiency, a variant of FGD type 4, is a very rare condition that may lead to high rates of mortality when the diagnosis and treatment occur late. Therefore, early diagnosis and treatment is essential for good outcomes.

Efficacy of suspended moxibustion stimulating Shenshu (BL23) and Guanyuan (CV4) on the amygdala-HPA axis in rats with kidney-deficiency symptom pattern induced by hydrocortisone.

To investigated the effects of suspended moxibustion stimulating Shenshu (BL23) and Guanyuan (CV4) acupoints on the amygdala and HPA axis in our rat model and elucidated the possible molecular mechanisms of moxibustion on kidney- deficiency symptom pattern (KYDS). Sixty male Sprague Dawley rats were randomly divided into a control group ( 12) and an experimental group ( 48). Rats in the experimental group were given intramuscular injections of hydrocortisone to establish a KYDS model. The 48 rats successfully modeled were then randomly divided into a model group (model, 12), a carbenoxolone intraperitoneal injection group (CBX, 12), a moxibustion group (moxi, 12), and a moxi + CBX group ( 12). In the moxi, the Shenshu (BL23) and Guanyuan (CV 4) acupoints were treated with moxibustion for 14 d. After treatment, measures were taken of serum levels of corticosterone (CORT), adrenocorticotropic hormone (ACTH), and corticotropin-releasing hormone (CRH). The expression of mineralocorticoid receptors (MRs), glucocorticoid receptors (GRs), 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1), CRH, and ACTH in the rats' amygdala, hypothalamus, or pituitary (as appropriate) was detected. Data were analyzed using one-way analysis of variance. Compared with those of the control group, the serum levels of CRH, ACTH, and CORT; the mRNA and protein expressions of MR, GR, and 11β-HSD1 in the amygdala; the mRNA and protein expressions of 11β-HSD1 in the hypothalamus; the CRH mRNA expression in the amygdala and hypothalamus; and the ACTH mRNA expression in the pituitary of the rats in the model group were all significantly decreased (0.05 or 0.01). After treatment with moxibustion, all the aforementioned observation indices except for 11β-HSD1 mRNA expression were ameliorated compared with those in the model group (0.05 or 0.01). Suspended moxibustion can effectively improve the serum levels of ACTH, CRH, and CORT and can up-regulate the mRNA and protein expressions of MR, GR, 11β-HSD1, CRH, and ACTH in the amygdala and hypothalamus of KYDS rats. This may be one of the molecular mechanisms with which moxibustion alleviates KYDS.

Epileptik ensefalopatide kullanılan adrenokortikotropik hormonun kemik mineral metabolizması ve adrenal yolak üzerine kısa dönem etkilerinin değerlendirilmesi

Background: We aimed to investigate the short-term effects of adrenocorticotropic hormone (ACTH) treatment on the adrenal pathway and bone metabolism in patients with epileptic encephalopathy.
 Methods: Two groups with 16 patients and 16 controls were formed. Before the treatment, all patients and controls were tested for bone and adrenal metabolism. Twenty doses of ACTH therapy were given to the patient group over 3 months. The tests on the patient group were repeated 1 month after the end of the treatment.
 Results: In the patient group, serum calcium, phosphorus and parathyroid hormone levels increased significantly after treatment compared with before treatment. Comparing the bone metabolism of the patient and control groups, urinary calcium/creatinine ratio was higher before treatment; serum phosphorus level, bone-specific alkaline phosphatase level and the urinary calcium/creatinine ratio were higher after treatment in the patient group. In the evaluation of the adrenal pathway, no significant differences were found between fasting serum glucose, sodium, potassium, cortisol and ACTH levels before and after treatment and in the comparison of the patient and control groups.
 Conclusion: Our study investigated the short-term effect of ACTH on the adrenal pathway and bone metabolism. The results show that ACTH treatment did not have a negative effect on the adrenal pathway in the early period but, its effects on bone metabolism have not been adequately clarified.

Anti-stress effects of Fameyes in in vitro and in vivo models of stresses

BackgroundFameyes (a mixture of Clematis mandshurica Rupr. extract (CMRE) and Erigeron annuus (L.) Pers. extract (EAPE)) containing scutellarin and chlorogenic acid as major components has been reported to relieve mental stress in human subjects, which is reflected in improved scores in psychometric tests measuring levels of depression, anxiety, well-being, and mental fitness. The aim of this study was to examine the anti-stress activity of Fameyes and to investigate the mechanisms of the anti-stress activity using in vitro and in vivo models of stresses.ResultsFirst, we tested the effect of Fameyes on corticosterone-induced cytotoxicity in SH-SY5Y cells (human neurofibroma cell lines). Corticosterone induced apoptosis and decreased cell viability and mitochondrial membrane potential, but treatment with Fameyes inhibited these cytotoxic effects in a dose-dependent manner. However, CMRE and EAPE (components of Fameyes) did not inhibit the cytotoxic effect of corticosterone individually. Next, we tested the effects of Fameyes on rats that were exposed to different kinds of stresses for four weeks. When the stressed rats were treated with Fameyes, their immobility time in forced swim and tail suspension tests decreased. A reduction was also observed in the serum levels of adrenocorticotropic hormone (ACTH) and corticosterone. Furthermore, upon oral administration of Fameyes, serum serotonin levels increased. These in vitro and in vivo results support the anti-stress effects of Fameyes.ConclusionsIn vitro experiments showed anti-stress effects of Fameyes in cell viability, apoptosis, and mitochondrial membrane potential. In addition, in vivo experiments using rats showed anti-stress effects of Fameyes in blood and tissue levels of ACTH, corticosterone, and serotonin, as well as the immobility time in the forced swim and tail suspension tests. However, we did not specifically investigate which ingredient or ingredients showed anti-stress effects, although we reported that Fameyes contained chlorogenic acid and scutellarin major ingredients.

Antidepressant effects of cherry leaf decoction on a chronic unpredictable mild stress rat model based on the Glu/GABA-Gln metabolic loop.

Cherry leaves (Prunus pseudocerasus Lindl. [Rosaceae]), a traditional Chinese herbal medicine, can regulate the factors closely related to depression including inflammatory cytokines, oxidative stress and blood glucose level. However, the antidepressant effects of cherry leaves and underlying neuromodulatory mechanisms remain relatively have not been elucidated explicitly. The present study investigated the antidepressant effects of cherry leaf decoction (CLD). The underlying neuromodulatory mechanism was explored by examining the glutamate (Glu)/γ-aminobutyric acid (GABA)-glutamine (Gln) metabolic loop. The chronic unpredictable mild stress (CUMS) rodent model was used in this study. The main flavonoids components of CLD were identified using high-performance liquid chromatography (HPLC). The antidepressant effects of CLD were assessed throughout behavioural tests including the bodyweight, sucrose preference test (SPT), forced swimming test (FPT) and tail suspension test (TST). Moreover, The baseline levels of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were quantified. The expression of proteins integrally involved in the Glu/GABA-Gln metabolic loop were observed and quantified by Western blotting, reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. This study found that CLD ameliorated depressive-like behaviours induced by CUMS. The increase of serum ACTH and CORT baseline levels induced by CUMS was also reversed after CLD intervention. Furthermore, CUMS reduced the expression of GAD65, GAD67, GLT-1, GS and GABAA and increased NMDAR1 levels in the rat hippocampus, which was normalized by CLD treatment. The findings demonstrated that CLD could ameliorate the depression-like behaviours induced by CUMS, potentially through the inhibition of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity and the regulation of Glu/GABA-Gln metabolic loop.

Effects of propofol combined with lidocaine on hemodynamics, serum adrenocorticotropic hormone, interleukin-6, and cortisol in children.

BACKGROUNDChildren are a unique patient population. Anesthesia for pediatric abdominal surgery has long been achieved mainly with intravenous amiodarone and propofol alone or combined with other anesthetics. The incidence of complications and postoperative adverse reactions is relatively high owing to the imperfect development of various protocols for children. Choosing the most appropriate anesthesia program is an important means of reducing adverse reactions.AIMTo explore the clinical value of propofol combined with lidocaine-assisted anesthesia in pediatric surgery.METHODSA total of 120 children who underwent abdominal surgery at our hospital from January 2016 to March 2018 were selected and divided into groups A and B using the random number table method, with 60 patients in each group. Group B received ketamine for anesthesia, while group A received ketamine, propofol, and lidocaine. The pre- and postoperative heart rate (HR); mean arterial pressure (MAP); arterial oxygen saturation (SpO2); serum adrenocorticotropic hormone (ACTH), interleukin-6 (IL-6), and cortisol (Cor) levels; restlessness score during the recovery period [Paediatric Anesthesia Emergence Delirium Scale (PAED)]; and adverse reactions were compared between the two groups.RESULTSThe HR, MAP, and SpO2 Level at five minutes before initiating anesthesia were compared between groups A and B, and the difference was not statistically significant (P > 0.05). At 10 and 20 minutes after anesthesia initiation, the HR and MAP were lower in group A compared with group B (P < 0.05). The differences in preoperative serum ACTH, IL-6, and Cor levels between groups A and B were not statistically significant (P > 0.05); however, the postoperative serum ACTH, IL-6, and Cor levels in group A were lower compared with group B (P < 0.05). Furthermore, the visual analog scale scores of group A at 2 h and 8 h postoperative were lower than those in group B, and the differences were statistically significant (P < 0.05). The mean PAED score in group A was lower than that in group B (P < 0.05), and the incidence of restlessness in group A was 23.33% lower than that in group B (36.67 %) (P < 0.05). The incidence of adverse reactions was lower in group A than in group B (6.25% vs 16.25%). CONCLUSIONThe anesthetic effect of propofol combined with lidocaine and ketamine in pediatric surgery was better than that of ketamine alone, and had less influence on hemodynamics and pediatric stress response indices, lower incidence of restlessness in the recovery period, and lower incidence of adverse reactions.

Acupoint compatibility effect and mechanism of Shenmen (HT7) and Sanyinjiao (SP6) in improving daytime fatigue and sleepiness of insomnia

To observe the acupoint compatibility effect of Shenmen (HT7) and Sanyinjiao (SP6) in improving daytime fatigue and sleepiness of insomnia, and its mechanism in regulating hypothalamic-pituitary-adrenal (HPA) axis and suprachiasmatic nucleus-pineal gland-melatonin (SCN-PG-MT) system. Ninety patients with insomnia were randomly divided into HT7, SP6 and HT7-SP6 (HT7 plus SP6) groups, with 30 cases in each group. Electroacupuncture (EA,5 Hz/25 Hz) was applied to HT7, SP6 or HT7-SP6 in each group for 30 min. The EA treatment was conducted once daily, 5 days a week for 2 weeks. Before and after treatment, the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were observed, separately. The contents of serum adrenocorticotrophic hormone (ACTH), cortisol (CS) and melatonin (MT) were detected by ELISA. Compared with before treatment, the sleep quality, sleep time, sleep efficiency, sleep disturbance, daytime dysfunction scores and total score of PSQI in the three groups after treatment were decreased (P<0.05), the time to fall asleep score of PSQI and total score of ESS were decreased in the SP6 and HT7-SP6 groups (P<0.05). After treatment, the sleep quality, time to fall asleep, sleep efficiency, daytime dysfunction scores, total score of PSQI and total score of ESS in the HT7-SP6 group were lower than those in the HT7 group (P<0.05), the sleep quality, sleep efficiency and total score of PSQI in the SP6 group were lower than those in the HT7 group (P<0.05). Compared with before treatment, the serum ACTH and CS levels in the three groups were decreased (P<0.05), and the serum MT levels in the SP6 and HT7-SP6 groups were increased (P<0.05). After treatment, the ACTH and CS levels in the HT7-SP6 group were lower than those in the HT7 group (P<0.05), and the serum MT levels in the SP6 and HT7-SP6 groups were higher than that in the HT7 group (P<0.05). The compatibility of HT7 and SP6 has a synergism effect on the improvement of night sleep quality and daytime fatigue and sleepiness of insomnia patients, the mechanism may be related with its function in down-regulating the serum ACTH and CS levels and increasing the serum MT content. SP6 has a better effect than HT7, and plays a major role in acupoint compatibility.

Probiotics (Bacillus clausii and Lactobacillus fermentum NMCC-14) Ameliorate Stress Behavior in Mice by Increasing Monoamine Levels and mRNA Expression of Dopamine Receptors (D1 and D2) and Synaptophysin.

Stress is a physiological consequence of the body to adversity. The gut–brain axis and probiotics are gaining interest to provide better treatment for stress and other neurological disorders. Probiotic (Lactobacillus fermentum NMCC-14 and Bacillus clausii, 1010 colony-forming unit/day/animal, per oral) effects were investigated in acute (up to day 7) and subacute (days 8–14) restraint-stressed and normal mice through behavioral paradigms (elevated plus maze: EPM, light dark box/dark light box: LDB, and open field test: OFT). Time spent in the open arms of the EPM, time spent in the light compartment of the LDB, and movable time and time spent in the center of the OFT were significantly (p ≤ 0.05, n = 5) increased in probiotic-treated restraint-stressed mice. Enzyme-linked immunoassay determined blood cortisol and adrenocorticotropic hormone (ACTH) levels, which were reduced significantly (p < 0.05, n = 5) in probiotic-treated restraint-stressed mice. Hematoxylin and eosin-stained hippocampal slides also showed less or no neurodegeneration in the probiotic-treated animals. High-performance liquid chromatography and quantitative polymerase chain reaction were performed to determine the monoamine levels and mRNA expression of dopamine receptor subtypes (D1 and D2) and synaptophysin in the mice hippocampus (HC) and prefrontal cortex (PFC). The dopamine, serotonin, and norepinephrine levels were also significantly (p < 0.05, n = 5) increased in the HC and PFC of probiotic-treated animal brains. Fold expression of mRNA of D1 and D2 (except HC, LF-S, day 14) receptors and synaptophysin was also significantly (p < 0.05, n = 5) increased in the same brain parts of probiotic-treated restraint-stressed mice. Comparing mice in the Lactobacillus fermentum NMCC-14 and Bacillus clausii groups to mice in the normal group, only a significant (p < 0.05, n = 5) decrease was observed in the serum ACTH and cortisol levels on day 14 in Bacillus clausii-treated mice, where all other parameters also showed improvement. In comparison, Bacillus clausii showed greater stress suppressant activity than Lactobacillus fermentum NMCC-14. However, both probiotic bacteria can be a better and safer therapeutic alternative for ailments than currently available drugs.

Immunomodulatory effects of fentanyl and morphine on DSS- and TNBS-induced colitis

Background Opioid prescription for inflammatory bowel disease (IBD)-related pain is on the rise. However, the use of strong opioids can result in severe complications, and even death, in IBD patients. This study aimed to define the role of fentanyl and morphine, two representative strong opioids, in the pathogenesis of dextran sodium sulphate (DSS)- and 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced colitis. Method DSS and TNBS models were induced in C57BL/6J and Balb/c mice, respectively. Disease activity index (DAI), histopathology, enzyme-linked immunosorbent assay (ELISA), multiplex ELISA, and flow cytometry were performed to evaluate the effects of fentanyl and morphine. Result Fentanyl exacerbated DSS- and TNBS-induced colitis, while morphine exhibited no significant immunomodulatory effect. Fentanyl and morphine had no obvious effects on the serum levels of adrenocorticotropic hormone (ACTH), glucocorticoid (GC), and prostaglandin E2 (PGE-2) in DSS and TNBS models. Fentanyl elevated the proportions of Th1 cells, μ-opioid receptor (MOR) + Th1 cells, and MOR + macrophages in the colonic mucosa of DSS-treated mice, and enhanced the proportions of Th1 cells, macrophages, MOR + Th1 cells, and MOR + macrophages in the colonic mucosa of TNBS-treated mice. We found that fentanyl upregulated the levels of inflammatory cytokines/chemokines in MOR + macrophages of the colonic lamina propria mononuclear cells (LPMCs) from DSS-treated mice, whereas it had no effect on the expression of most inflammatory cytokines/chemokines in MOR + macrophages in the colonic LPMCs from TNBS-treated mice. Conclusion Our findings suggest that fentanyl exacerbates murine colitis via Th1 cell- and macrophage-mediated mechanisms, while morphine exhibits no significant immunomodulatory effect.