In this report, the protective effect and molecular mechanism of Chaihu Shugan San-containing serum on corticosterone(CORT)-induced mitochondrial damage in pheochromocytoma(PC12) cells was studied based on CORT-induced rat PC12 cell model. The cultured cells were divided into five groups: blank control group, CORT group(400 μmol·L~(-1) CORT), Chaihu Shugan San-containing serum group(400 μmol·L~(-1) CORT + 10% Chaihu Shugan San-containing serum), control serum group(400 μmol·L~(-1) CORT + 10% control serum), and fluoxetine group(400 μmol·L~(-1) CORT + 10% fluoxetine-containing serum). The study was carried out by cell activity detection, mitochondrial morphology observation, membrane potential measurement, energy metabolism analysis, and mitochondrial dynamics-related protein detection. The results showed that CORT treatment significantly reduced the survival rate of PC12 cells, altered mitochondrial morphology, and decreased mitochondrial membrane potential and adenosine triphosphate(ATP) synthetic rate. Both Chaihu Shugan San-and fluoxetine-containing serum significantly increased the survival rate of CORT-treated PC12 cells and the ATP synthetic rate in the mitochondria. Unlike fluoxetine, Chaihu Shugan San-containing serum significantly inhibited the decrease in mitochondrial membrane potential caused by CORT and increased the oxygen consumption rate(OCR) values of both mitochondrial maximum respiration and reserve respiration capacity. Western blot analysis showed that CORT induced upregulated protein expressions of dynamin-related protein 1(Drp1) and peroxisome proliferator-activated receptor gamma co-activator 1α(PGC-1α) in PC12 cells and specific protein expression of optic atrophy protein 1(OPA1), yet it repressed the protein expressions of silent information regulator 1(SIRT1) and mitochondrial fusion protein 1(Mfn1) in PC12 cells. Both Chaihu Shugan San-and fluoxetine-containing serum significantly inhibited the protein expression of Drp1. However, only Chaihu Shugan San-containing serum could significantly inhibit the CORT-induced upregulation protein of PGC-1α. RESULTS:: herein suggest that Chaihu Shugan San-containing serum can alleviate CORT-induced damage in PC12 cells, which may be related to the mitochondrial fragmentation/lipid peroxidation protection by Drp1 inhibition, as well as mitochondrial dynamics and energy metabolism mediated by PGC-1α/SIRT1 signaling pathway.
Animals ; PC12 Cells ; Rats ; Mitochondrial Dynamics/drug effects* ; Mitochondria/metabolism* ; Corticosterone/adverse effects* ; Membrane Potential, Mitochondrial/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Protective Agents/pharmacology* ; Cell Survival/drug effects*

BACKGROUND: In response to growing concerns about the health effects of quasi-millimeter waves (qMMW) used in 5th-generation wireless systems, conservative whole-body exposure thresholds based on indirect evidence have been proposed. The guidelines define a whole-body average specific absorption rate (WBA-SAR) of 4 W/kg which causes a 1 °C increase in core temperature, as the operational threshold for adverse health effects. To address the lack of direct evidence, we recently reported that a 30-minute exposure to qMMW at 4.6 W/kg resulted in a 1 °C increase in rat core temperature. Here, we further analyzed the near-threshold stress response for the first time, using biological samples from the aforementioned and additional experiments. METHODS: A total of 59 young Sprague-Dawley rats (240-322 g) were exposed to 28 GHz for 40 minutes at WBA-SARs of 0, 3.7, and 7.2 W/kg, under normal (22.5 °C, 45-55% humidity), and heat (32 °C, 70% humidity) conditions. Rats were restrained in acrylic holders for dose control. We repeatedly measured serum and urinary biomarkers of stress response, aggregated the data, and analyzed them using a single statistical mixed model to subtract the effects of sham exposure and between-subject variation. RESULTS: Sham exposure induced stress responses, suggesting an effect of restraint. After the subtraction of the sham exposure effect, 28 GHz appeared to induce stress responses as evidenced by elevated serum-free corticosterone 1 or 3 days after the exposure, which was more evident in animals with a change in rectal temperature exceeding 1 °C. Urinary-free catecholamines demonstrated an inhibitory property of 28 GHz frequency exposure on the stress response as evidenced by noradrenaline on the day of exposure. Heat exposure enhanced this effect, suggesting a possible role of noradrenaline in heat dissipation by promoting cutaneous blood flow, a notion supported by the correlation between noradrenaline levels and tail surface temperature, a critical organ for heat dissipation. CONCLUSIONS This study is the first to demonstrate that qMMW whole-body exposure can alter the stress response as indicated by corticosterone and noradrenaline at near-threshold levels. Our findings may provide insight into the biological basis of the whole-body exposure thresholds in the international guidelines.
Animals ; Rats ; Rats, Sprague-Dawley ; Male ; Restraint, Physical ; Stress, Physiological/radiation effects* ; Corticosterone/blood* ; Biomarkers/blood* ; Microwaves/adverse effects*

OBJECTIVE: To explore the inhibitory effects of Nardostachys Jatamansi DC. volatile oil (NJVO) on psychological factors substance P (SP)/cortisol (CORT)-induced hyperpigmentation. METHODS: The model of psychologically-induced hyperpigmentation of B16F10 cells was created using SP (10 nmol/L) + CORT (10 µmol/L) for 72 h. The levels of melanin content, tyrosinase (TYR) activity using NaOH lysis and L-dihydroxyphenylalanine (L-DOPA) oxidation methods were assessed, respectively. The effect of NJVO on SP/CORT-induced normal human skin tissue pigmentation was detected by Masson staining. Protein expressions of tyrosinase-related protein 1 (TRP-1), tyrosinase-relative protein 2 (DCT), and microphthalmia-associated transcription factor were determined using Western blot. The melanosome number, maturation, and melanosomal structure changes were detected through transmission electron microscopy and immunofluorescence experiments. In vivo, zebrafish pigment content was evaluated in SP/CORT-induced zebrafish hyperpigmentation model. RESULTS: NJVO significantly reduced the melanin content (P<0.01) and inhibited tyrosinase activity (P<0.01), the pigmentation of the normal skin tissue in the NJVO group was significantly lower than that in the SP/CORT group (P<0.05). And NJVO considerably downregulated expressions of melanogenesis-related proteins (TYR, TRP-1, DCT) in cells (P<0.01). In addition, the number of melanosomes was decreased and the dentrites formation of B16F10 cells was inhibited after NJVO treatment (P<0.01). In vivo, NJVO significantly reduced the pigment content in the zebrafish body (P<0.01). CONCLUSION NJVO effectively reversed SP/CORT-induced hyperpigmentation by suppressing the activity and expression of TYR and TRPs and inhibiting melanosome maturation in mouse B16F10 melanoma cells.
Animals ; Hyperpigmentation/psychology* ; Zebrafish ; Oils, Volatile/therapeutic use* ; Melanins/metabolism* ; Humans ; Monophenol Monooxygenase/metabolism* ; Mice ; Nardostachys/chemistry* ; Substance P ; Hydrocortisone ; Skin Pigmentation/drug effects* ; Cell Line, Tumor ; Melanosomes/ultrastructure* ; Microphthalmia-Associated Transcription Factor/metabolism* ; Melanoma, Experimental ; Oxidoreductases/metabolism* ; Intramolecular Oxidoreductases/metabolism*

Empathy is crucial for communication and survival for individuals. Whether empathy in pain contagion shows sex differences and its underlying mechanisms remain unclear. Here, we report that pain contagion can occur in stranger female rats, but not in stranger males. Blocking oxytocin receptors in the anterior cingulate cortex (ACC) suppressed pain contagion in female strangers, while oxytocin administration induced pain contagion in male strangers. In vitro, corticosterone reduces neuronal activation by oxytocin. During male stranger interactions, higher corticosterone decreased oxytocin receptor-positive neuronal activity in the ACC, suppressing pain contagion. These findings highlight the role of oxytocin in pain contagion and suggest that sex differences in empathy may be determined by the balance of oxytocin and corticosterone in the ACC. This study suggests an approach for the treatment of certain mental disorders associated with abnormal empathy, such as autism and depression.
Animals ; Oxytocin/pharmacology* ; Gyrus Cinguli/drug effects* ; Male ; Female ; Corticosterone/pharmacology* ; Empathy/drug effects* ; Sex Characteristics ; Receptors, Oxytocin/antagonists & inhibitors* ; Pain/psychology* ; Rats ; Rats, Sprague-Dawley ; Neurons/metabolism*

OBJECTIVE: To explore whether hydrocortisone can improve the prognosis of patients with severe community-acquired pneumonia (sCAP) by Meta-analysis. METHODS: Randomized controlled trial (RCT) on hydrocortisone in the treatment of sCAP were extracted from the database including PubMed, Cochrane library, Web of Science, and Embase, and the search time was up to April 29, 2023. The patients in the standard treatment group received standard treatment such as antibiotics and supportive care, while those in the hydrocortisone group received hydrocortisone treatment on the basis of standard treatment. Meta-analysis was used to compare the mortality, duration of mechanical ventilation, mechanical ventilation rate and incidence of adverse reactions (hyperglycemia, gastrointestinal bleeding, secondary infection) between the two groups. The risk of literature bias was assessed. The studies that might have publication bias were corrected by the subtraction and complementation method. At the same time, trial sequential analysis (TSA) was conducted. RESULTS: A total of 5 RCTs involving 1 031 patients were finally enrolled, including 494 patients in the standard treatment group and 537 patients in the hydrocortisone group. Among the 5 studies, the research site of 2 studies was in the mixed ward. Considering the inclusion characteristics of the study population, there was doubt whether its research object was sCAP patients, which might have a certain impact on the results and introduce potential bias. Meta-analysis showed that the mortality in the hydrocortisone group was significantly lower than that in the standard treatment group [6.0% vs. 14.0%; odds ratio (OR) = 0.38, 95% confidence interval (95%CI) was 0.25-0.59, P < 0.01; I² = 9%]. The studies that were asymmetric were corrected by the reduction and supplementation method. Even after filling the missing studies, hydrocortisone could still reduce the death risk of the patient (OR = 0.49, 95%CI was 0.32-0.73, P < 0.01; I² = 31%). TSA showed that the average mortality of the standard treatment group was about 14.0%, and that of the hydrocortisone group was about 6.0%, with a relative risk reduction (RRR) = 57%. The calculated sample size was 699 cases, and the actual sample size was 1 031 cases. The actual sample size exceeded the required sample size, and the Z-curve crossed the O'Brien-Fleming boundary and the curve corresponding to P = 0.05, it meant that hydrocortisone could effectively reduce the mortality of sCAP. Compared with the standard treatment group, no statistical difference in the duration of mechanical ventilation was found in the hydrocortisone group [mean difference (MD) = -3.26, 95%CI was -6.72-0.21, P = 0.07; I² = 0%], but the 8-day mechanical ventilation rate was significantly lowered (19.5% vs. 55.4%; OR = 0.24, 95%CI was 0.12-0.45, P < 0.01; I² = 0%), and also no significantly difference was found in the incidence of hyperglycemia (54.3% vs. 44.6%, OR = 1.26, 95%CI was 0.56-2.84, P = 0.58; I² = 61%), gastrointestinal bleeding (2.5% vs. 3.6%; OR = 0.70, 95%CI was 0.34-1.46, P = 0.34; I² = 0%) and secondary infection (9.2% vs. 11.5%; OR = 0.46, 95%CI was 0.06-3.35, P = 0.45; I² = 53%). CONCLUSION Hydrocortisone can reduce the mortality rate of sCAP patients, decrease their need for mechanical ventilation, and does not increase the risk of hyperglycemia, gastrointestinal bleeding, or secondary infections.
Humans ; Hydrocortisone/therapeutic use* ; Community-Acquired Infections/drug therapy* ; Pneumonia/drug therapy* ; Randomized Controlled Trials as Topic ; Respiration, Artificial ; Community-Acquired Pneumonia

Adrenocortical carcinoma (ACC) accounts for 0.05-2% of all malignant tumors. Forty-five percent of ACCs with secretory function have excess glucocorticoids alone and only less than 1% secrete aldosterone.

This is a case of a 44-year-old Filipino female with hypertension and a 12-year-history of an incidentaloma of the left adrenal gland, with recent-onset complaints of increasing abdominal girth, purple striae, amenorrhea, moon facies and a dorsocervical fat pad. Laboratory findings revealed low potassium levels, non-suppressed cortisol on dexamethasone test suggesting Cushing’s syndrome and elevated aldosterone-renin ratio and plasma aldosterone concentration pointing to primary hyperaldosteronism. A computed tomography scan revealed a left-sided adrenal mass measuring approximately 23 cm in largest diameter suggestive of carcinoma without metastasis or lymph node involvement. Complete resection via open adrenalectomy was performed and histopathologic assessment revealed Adrenocortical Carcinoma with Weiss score of 4. The Ki-67 proliferative index was found to be >20%. Radiotherapy was done as an adjuvant treatment.

Although rare, co-secretion of cortisol and aldosterone can occur in functional tumors of adrenocortical carcinoma. Malignancy should always be considered in patients who present with a history of a unilateral adrenal mass and/ or in those with signs and symptoms of adrenal hormone excess. Thus, a proper assessment derived from a thorough medical history, physical examination and laboratory work-up is warranted in patients with an adrenal mass to ascertain the diagnosis and provide adequate management.

Humans ; Hyperaldosteronism/therapy* ; Aldosterone ; Hypertension

Objective: To explore the value of catheter-based adrenal ablation in treating Cushing's syndrome (CS)-associated hypertension. Methods: A clinical study was conducted in patients with CS, who received catheter-based adrenal ablation between March 2018 and July 2023 in Daping Hospital. Parameters monitored were blood pressure (outpatient and 24-hour ambulatory), body weight, clinical characteristics, serum cortisol and adrenocorticotropic hormone (ACTH) at 8 am, 24-hour urinary free cortisol (24 h UFC), fasting blood glucose and postoperative complications. Procedure effectiveness was defined as blood pressure returning to normal levels (systolic blood pressure<140 mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure<90 mmHg), cortisol and 24 h UFC returning to normal and improvement of clinical characteristics. The parameters were monitored during follow up in the outpatient department at 1, 3, 6, and 12 months after catheter-based adrenal ablation. Results: A total of 12 patients (aged (40.0±13.2) years) were reviewed. There were 5 males, with 5 cases of adenoma and 7 with hyperplasia from imaging studies. Catheter-based adrenal ablation was successful in all without interruption or surgical conversion. No postoperative complication including bleeding, puncture site infection, adrenal artery rupture or adrenal bleeding was observed. The mean follow up was 28 months. Compared to baseline values, body weight declined to (59.48±11.65) kg from (64.81±10.75) kg (P=0.008), fasting blood glucose declined to (4.54±0.83) mmol from (5.53±0.99) mmol (P=0.044), outpatient systolic blood pressure declined to (128±21) mmHg from (140±19) mmHg (P=0.005), diastolic blood pressure declined to (78±10) mmHg from (86±11) mmHg (P=0.041), and the mean ambulatory daytime diastolic blood pressure declined to (79±12) mmHg from (89±8) mmHg (P=0.034). Catheter-based adrenal ablation in 8 patients was defined as effective with their 24 h UFC significantly reduced after the procedure (1 338.41±448.06) mmol/L from (633.66±315.94) mmol/L, P=0.011). The change of 24 h UFC between the effective treatment group and ineffective group was statistically significant (P=0.020). The postoperative systolic blood pressure in the treated adenoma group was significantly lower than those of hyperplasia group (112±13) mmHg vs. (139±20) mmHg, P=0.026). Conclusions: For patients with CS-associated hypertension who are unwilling or unable to undergo surgical treatment, catheter-based adrenal ablation could improve the blood pressure and cortisol level. Catheter-based adrenal ablation could be a safe, effective, and minimally invasive therapy. However, our results still need to be validated in further large-scale studies.
Male ; Humans ; Cushing Syndrome/complications* ; Hydrocortisone ; Adrenal Gland Neoplasms/surgery* ; Feasibility Studies ; Blood Glucose ; Hyperplasia/complications* ; Hypertension/complications* ; Adenoma/complications* ; Body Weight ; Catheters/adverse effects*

Humans ; Hyperaldosteronism/therapy* ; Aldosterone ; Hypertension

Objective: To explore the value of catheter-based adrenal ablation in treating Cushing's syndrome (CS)-associated hypertension. Methods: A clinical study was conducted in patients with CS, who received catheter-based adrenal ablation between March 2018 and July 2023 in Daping Hospital. Parameters monitored were blood pressure (outpatient and 24-hour ambulatory), body weight, clinical characteristics, serum cortisol and adrenocorticotropic hormone (ACTH) at 8 am, 24-hour urinary free cortisol (24 h UFC), fasting blood glucose and postoperative complications. Procedure effectiveness was defined as blood pressure returning to normal levels (systolic blood pressure<140 mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure<90 mmHg), cortisol and 24 h UFC returning to normal and improvement of clinical characteristics. The parameters were monitored during follow up in the outpatient department at 1, 3, 6, and 12 months after catheter-based adrenal ablation. Results: A total of 12 patients (aged (40.0±13.2) years) were reviewed. There were 5 males, with 5 cases of adenoma and 7 with hyperplasia from imaging studies. Catheter-based adrenal ablation was successful in all without interruption or surgical conversion. No postoperative complication including bleeding, puncture site infection, adrenal artery rupture or adrenal bleeding was observed. The mean follow up was 28 months. Compared to baseline values, body weight declined to (59.48±11.65) kg from (64.81±10.75) kg (P=0.008), fasting blood glucose declined to (4.54±0.83) mmol from (5.53±0.99) mmol (P=0.044), outpatient systolic blood pressure declined to (128±21) mmHg from (140±19) mmHg (P=0.005), diastolic blood pressure declined to (78±10) mmHg from (86±11) mmHg (P=0.041), and the mean ambulatory daytime diastolic blood pressure declined to (79±12) mmHg from (89±8) mmHg (P=0.034). Catheter-based adrenal ablation in 8 patients was defined as effective with their 24 h UFC significantly reduced after the procedure (1 338.41±448.06) mmol/L from (633.66±315.94) mmol/L, P=0.011). The change of 24 h UFC between the effective treatment group and ineffective group was statistically significant (P=0.020). The postoperative systolic blood pressure in the treated adenoma group was significantly lower than those of hyperplasia group (112±13) mmHg vs. (139±20) mmHg, P=0.026). Conclusions: For patients with CS-associated hypertension who are unwilling or unable to undergo surgical treatment, catheter-based adrenal ablation could improve the blood pressure and cortisol level. Catheter-based adrenal ablation could be a safe, effective, and minimally invasive therapy. However, our results still need to be validated in further large-scale studies.
Male ; Humans ; Cushing Syndrome/complications* ; Hydrocortisone ; Adrenal Gland Neoplasms/surgery* ; Feasibility Studies ; Blood Glucose ; Hyperplasia/complications* ; Hypertension/complications* ; Adenoma/complications* ; Body Weight ; Catheters/adverse effects*