Low resting metabolic rate and increased hunger due to ß-MSH and ß-endorphin deletion in a canine model.

Mutations that perturb leptin-melanocortin signaling are known to cause hyperphagia and obesity, but energy expenditure has not been well studied outside rodents. We report on a common canine mutation in pro-opiomelanocortin (POMC), which prevents production of ß-melanocyte-stimulating hormone (ß-MSH) and ß-endorphin but not α-MSH; humans, similar to dogs, produce α-MSH and ß-MSH from the POMC propeptide, but rodents produce only α-MSH. We show that energy expenditure is markedly lower in affected dogs, which also have increased motivational salience in response to a food cue, indicating increased wanting or hunger. There was no difference in satiety at a modified ad libitum meal or in their hedonic response to food, nor disruption of adrenocorticotropic hormone (ACTH) or thyroid axes. In vitro, we show that ß-MSH signals comparably to α-MSH at melanocortin receptors. These data implicate ß-MSH and ß-endorphin as important in determining hunger and moderating energy expenditure and suggest that this role is independent of the presence of α-MSH.

The Melanocortin and Endorphin Neuropeptides in Patients with Restless Legs Syndrome.

OBJECTIVE: Based upon similarities between the urge to move and sensory discomfort of restless legs syndrome (RLS) and properties of melanocortin hormones, including their incitement of movement and hyperalgesia, we assessed plasma and cerebrospinal fluid (CSF) α-melanocyte-stimulating hormone (α-MSH) and ß-endorphin in RLS patients and controls. METHODS: Forty-two untreated moderate-to-severe RLS patients and 44 matched controls underwent venipuncture at 19:00, 20:30, and 22:00; 37 RLS and 36 controls had lumbar puncture at 21:30. CSF and plasma were analyzed for pro-opiomelanocortin (POMC), adrenocorticotropin hormone (ACTH), α-MSH, ß-MSH, and ß-endorphin by immunoassay. RLS severity was assessed by International RLS Study Group Severity Scale. RESULTS: RLS participants were 52.7 ± 12.0 years old, 61.9% were women, 21.4% had painful RLS, and RLS severity was 24.8 ± 9.0. Controls had similar age and sex. Plasma ACTH, α-MSH, and ß-endorphin were similar between groups. Plasma POMC was significantly greater in RLS than controls (17.0 ± 11.5 vs 12.7 ± 6.1fmol/ml, p = 0.048). CSF ACTH was similar between groups. CSF ß-MSH was significantly higher in painful than nonpainful RLS or controls (48.2 ± 24.8 vs 32.1 ± 14.8 vs 32.6 ± 15.2pg/ml, analysis of variance [ANOVA] p = 0.03). CSF α-MSH was higher in RLS than controls (34.2 ± 40.9 vs 20.3 ± 11.0pg/ml, p = 0.062). CSF ß-EDP was lowest in painful RLS, intermediate in nonpainful RLS, and highest in controls (8.0 ± 3.4 vs 10.8 ± 3.1 vs 12.3 ± 5.0pg/ml, ANOVA p = 0.049). The ratio of the sum of CSF α- and ß-MSH to CSF ß-endorphin was highest, intermediate, and lowest in painful RLS, nonpainful RLS, and controls (p = 0.007). INTERPRETATION: CSF ß-MSH is increased and CSF ß-endorphin decreased in RLS patients with painful symptoms. ANN NEUROL 2024;95:688-699.

The endogenous opioid system in the medial prefrontal cortex mediates ketamine's antidepressant-like actions.

Recent studies have implicated the endogenous opioid system in the antidepressant actions of ketamine, but the underlying mechanisms remain unclear. We used a combination of pharmacological, behavioral, and molecular approaches in rats to test the contribution of the prefrontal endogenous opioid system to the antidepressant-like effects of a single dose of ketamine. Both the behavioral actions of ketamine and their molecular correlates in the medial prefrontal cortex (mPFC) are blocked by acute systemic administration of naltrexone, a competitive opioid receptor antagonist. Naltrexone delivered directly into the mPFC similarly disrupts the behavioral effects of ketamine. Ketamine treatment rapidly increases levels of ß-endorphin and the expression of the µ-opioid receptor gene (Oprm1) in the mPFC, and the expression of gene that encodes proopiomelanocortin, the precursor of ß-endorphin, in the hypothalamus, in vivo. Finally, neutralization of ß-endorphin in the mPFC using a specific antibody prior to ketamine treatment abolishes both behavioral and molecular effects. Together, these findings indicate that presence of ß-endorphin and activation of opioid receptors in the mPFC are required for the antidepressant-like actions of ketamine.

The opioid peptide ß-endorphin interferes with the pituitary-testis axis in the Mozambique tilapia Oreochromis mossambicus.

Although the involvement of ß-endorphin (ß-ERP) in vertebrate reproduction has been suggested, its role in testicular activity is not clear in fish. We describe the influence of ß-ERP on spermatogenesis in a cichlid fish in the present paper. In comparison to the control group, the administration of ß-ERP (3 µg) caused a significant increase in the number of spermatogonia-A and spermatids. Following treatment with ß-ERP (6 µg), a significant increase in the number of spermatogonia-A was observed, whereas the numbers of all the other germ cells, excluding spermatogonia-B, significantly decreased in comparison to those in the control group. In addition, treatment of fish with 6 µg ß-ERP resulted in a significant reduction in the dimensions of the lumen and seminiferous lobules, the level of immunopositive androgen receptor (AR) expression in Sertoli cells, and the percentage of luteinizing hormone (LH) immunolabeled in the pituitary compared to those in the control group or the group treated with 3 µg ß-ERP. In contrast, the intensity of AR immunoreactivity and the percentage of LH immunolabeling were substantially increased in fish treated with 3 µg ß-ERP compared to those in the control group. These findings reveal for the first time that a low dose of ß-ERP stimulates the recruitment of spermatogonia as well as spermateleosis, whereas a high concentration affects the recruitment of germ cells prior to meiotic division in tilapia. These results suggest that ß-ERP exerts modulatory effects at the testicular and hypophysial levels through alterations in AR expression and LH secretory activity, respectively, in teleosts.

Review of the role of the endogenous opioid and melanocortin systems in the restless legs syndrome.

Restless legs syndrome (RLS) is responsive to opioid, dopaminergic and iron-based treatments. Receptor blocker studies in RLS patients suggest that the therapeutic efficacy of opioids is specific to the opioid receptor and mediated indirectly through the dopaminergic system. An RLS autopsy study reveals decreases in endogenous opioids, ß-endorphin and perhaps Met-enkephalin in the thalamus of RLS patients. A total opioid receptor knock-out (mu, delta and kappa) and a mu-opioid receptor knock-out mouse model of RLS show circadian motor changes akin to RLS and, although both models show sensory changes, the mu-opioid receptor knock mouse shows circadian sensory changes closest to those seen in idiopathic RLS. Both models show changes in striatal dopamine, anaemia and low serum iron. However, only in the total receptor knock-out mouse do we see the decreases in serum ferritin that are normally found in RLS. There are also decreases in serum iron when wild-type mice are administered a mu-opioid receptor blocker. In addition, the mu-opioid receptor knock-out mouse also shows increases in striatal zinc paralleling similar changes in RLS. Adrenocorticotropic hormone and α-melanocyte stimulating hormone are derived from pro-opiomelanocortin as is ß-endorphin. However, they cause RLS-like symptoms and periodic limb movements when injected intraventricularly into rats. These results collectively suggest that an endogenous opioid deficiency is pathogenetic to RLS and that an altered melanocortin system may be causal to RLS as well.

ß-Endorphin influences sedative and ataxic effects of alcohol.

Beta-endorphin (ß-E) is an opioid peptide linked to the behavioral effects of ethanol. For example, ß-E provides negative feedback to inhibit the hypothalamic-pituitary-adrenal (HPA) stress axis, and neuroadaptation of this system to ethanol may facilitate sex differences in disordered drinking. Locomotor sensitivity to ethanol may also influence the risk for addiction; however, the role of ß-E in psychomotor effects of ethanol is not fully understood. We examined the role of ß-E and sex on locomotor effects of ethanol using adult male and female wild-type C57BL/6J and ß-E deficient B6.129S2-Pomctm1Low/J mice in a parallel rod floor apparatus following 0.75 or 2.0 g/kg ethanol. Beginning 15 min after intraperitoneal injection, we recorded foot slips, distance traveled, slips per meter, first instance of immobility, and total time spent off-balance (lying on the floor) over 15 min, and collected blood for analysis of ethanol concentration 60 min after injection. Overall, ß-E deficient mice were more sedated and ataxic following ethanol; at the lower dose they slipped more frequently and had a higher rate of slips per meter traveled. At the higher dose, ß-E deficient mice were predominantly sedated, slipping less frequently, and traveling less, as well as spending more time off-balance and becoming immobile sooner. Genotype interacted with sex in that male ß-E deficient mice slipped more frequently than their female counterparts, suggesting that ß-E may elicit sex-dependent effects of ethanol-induced ataxia. Blood ethanol concentration did not differ between any group, suggesting that behavioral differences result from altered sensitivity to ethanol. Our data support the contention that ß-E modulates the locomotor effects of ethanol and may influence ataxia in a sex-dependent manner. These findings help elucidate the role of ß-E in diverging behavioral responses to ethanol and may aid the development of targeted treatments for alcohol use disorders.

Effect of transcutaneous electrical acupoint stimulation on remifentanil dosage during craniotomy aneurysm clipping: a prospective, randomized controlled study.

BACKGROUND: Craniotomy aneurysm clipping is one of the main treatments for intracranial aneurysm (IA). Endotracheal intubation and intraoperative operation may induce dramatic hemodynamic fluctuations and increase the risk of aneurysm rupture. Intraoperative high-dose opioid use is the main measure to reduce the intraoperative stress response, but it increases the incidence of complications such as postoperative vomiting and delayed awakening. Transcutaneous electrical acupoint stimulation (TEAS) stimulates ß-endorphin expression levels and reduces opioid requirements. In this study, we aimed to assess the effects of TEAS on remifentanil dosage and oxidative stress (OS) in craniotomy aneurysm clipping. METHOD: Forty-two patients with craniotomy aneurysm clipping were randomized into two groups: the TEAS group (T group) and the sham TEAS group (S group). "Hegu" (LI4), "Neiguan" (PC6) and "Zusanli" points (ST36) were selected, and a "HANS" percutaneous acupoint electrical stimulator was used for intervention 30 min before anesthesia induction until the end of the operation. The primary outcome was intraoperative remifentanil dosage. The secondary outcomes were intraoperative propofol dosage, mean arterial pressure (MAP) and heart rate (HR) 5 min before the TEAS intervention (T0), 5 min before head holder pinning (T1), immediately after pinning (T2), 5 min before craniotomy (T3), immediately after craniotomy (T4), at craniotomy (T5), and at the end of surgery (T6), as well as serum ß-endorphin levels at T1, T2 and T6 and neuron-specific enolase (NSE), S100ß, superoxide dismutase (SOD) and malondialdehyde (MDA) levels at T1, T2 and 24 h after surgery (T7). RESULTS: The dosage of remifentanil in the T group was reduced compared to that in the S group (P < 0.05). At T2, T4 and T5, the MAP and HR in the T group were lower than those in the S group (P < 0.05). At T2 and T7, the levels of NSE, S100ß and MDA in group T were lower than those in group S (P < 0.05), while the SOD levels in group T were higher than those in group S (P < 0.05). CONCLUSIONS: The use of TEAS can reduce the dosage of remifentanil and reduce hemodynamic fluctuations during craniotomy aneurysm clipping. It reduces the occurrence of OS and central nervous system damage during surgery and has a certain brain protective effect. TRIAL REGISTRATION: ChiCTR2100052353. https://www.chictr.org.cn/about.html .

ß-endorphin suppresses ultraviolet B irradiation-induced epidermal barrier damage by regulating inflammation-dependent mTORC1 signaling.

Solar ultraviolet B (UVB) radiation triggers excessive inflammation, disrupting the epidermal barrier, and can eventually cause skin cancer. A previous study reported that under UVB irradiation, epidermal keratinocytes synthesize the proopiomelanocortin-derived peptide ß-endorphin, which is known for its analgesic effect. However, little is known about the role of ß-endorphin in UVB-exposed skin. Therefore, in this study, we aimed to explore the protective role of ß-endorphin against UVB irradiation-induced damage to the skin barrier in normal human keratinocytes (NHKs) and on a human skin equivalent model. Treatment with ß-endorphin reduced inflammatory responses in UVB-irradiated NHKs by inactivating the NF-κB signaling pathway. Additionally, we found that ß-endorphin treatment reversed UVB-induced abnormal epidermal proliferation and differentiation in NHKs and, thus, repaired the skin barrier in UVB-treated skin equivalents. The observed effects of ß-endorphin on UVB-irradiated NHKs were mediated via blockade of the Akt/mTOR signaling pathway. These results reveal that ß-endorphin might be useful against UVB-induced skin injury, including the disruption of the skin barrier function.

Curative effect of wrist-ankle acupuncture on postpartum abdominal pain and its influence on serum ß-EP level in puerpera. / è •è¸é’ˆæ²»ç–—äº§åŽè ¹ç—›çš„ä¸´åºŠç–—æ•ˆåŠå¯¹äº§å¦‡è¡€æ¸ ß-EP水平的影响.

OBJECTIVES: To observe the clinical effect of wrist-ankle acupuncture on postpartum abdominal pain and its influence on serum beta-endorphin (ß-EP) level in puerpera. METHODS: Seventy patients with postpartum abdominal pain were randomly divided into an acupuncture + herbal medication group (35 cases, 1 case dropped out) and a herbal medication group (35 cases, 2 cases dropped out). In the herbal medication group, 1 day after delivery, modified shenghua decoction was taken orally, one dose a day. In the acupuncture + herbal medication group, on the basis of herbal medication, wrist-ankle acupuncture was given at the Lower 1 and Lower 2 of the ankles, once daily. The duration of treatment was 3 days in the two groups. Before and after treatment, the score of visual analogue scale (VAS) for pain, serum ß-EP level, uterine fundus height, postpartum conditions of lochia and the uterine recovery at 42 days postpartum were compared in the patients of the two groups. RESULTS: At each time point after treatment (24 h, 48 h and 72 h after delivery), VAS scores and the uterine fundus height were reduced as compared with those before treatment (2 h after delivery) in the two groups (P<0.05); these indexes in the acupuncture + herbal medication group were lower than those in the herbal medication group (P<0.05). After treatment (72 h after delivery), ß-EP levels in the serum were increased when compared with those before treatment in the two groups (P<0.05), and the ß-EP level in the acupuncture + herbal medication group was higher than that in the herbal medication group (P<0.05). The volume of postpartum lochia discharge in the acupuncture + herbal medication group was higher than that in the herbal medication group (P<0.05), while the duration of postpartum lochia discharge and the total time of lochia discharge were shorter (P<0.05). Regarding the recovery of the uterus at 42 days postpartum, there was no statistical significance between the two groups (P>0.05). CONCLUSIONS: Wrist-ankle acupuncture obviously reduces the degree of postpartum abdominal pain and promotes the lochia discharge and the uterine recovery. The effect mechanism may be related to the up-regulation of serum ß-EP level and the increase of pain threshold so that analgesia is obtained.

Epigenetic regulation of beta-endorphin synthesis in hypothalamic arcuate nucleus neurons modulates neuropathic pain in a rodent pain model.

Although beta-endorphinergic neurons in the hypothalamic arcuate nucleus (ARC) synthesize beta-endorphin (ß-EP) to alleviate nociceptive behaviors, the underlying regulatory mechanisms remain unknown. Here, we elucidated an epigenetic pathway driven by microRNA regulation of ß-EP synthesis in ARC neurons to control neuropathic pain. In pain-injured rats miR-203a-3p was the most highly upregulated miRNA in the ARC. A similar increase was identified in the cerebrospinal fluid of trigeminal neuralgia patients. Mechanistically, we found histone deacetylase 9 was downregulated following nerve injury, which decreased deacetylation of histone H3 lysine-18, facilitating the binding of NR4A2 transcription factor to the miR-203a-3p gene promoter, thereby upregulating miR-203a-3p expression. Further, increased miR-203a-3p was found to maintain neuropathic pain by targeting proprotein convertase 1, an endopeptidase necessary for the cleavage of proopiomelanocortin, the precursor of ß-EP. The identified mechanism may provide an avenue for the development of new therapeutic targets for neuropathic pain treatment.

[Efficacy and safety of high-voltage pulsed radiofrequency combined with pregabalin on severe thoracic postherpetic neuralgia].

Objective: To investigate the efficacy and safety of high-voltage pulse radiofrequency combined with pregabalin on severe thoracic postherpetic neuralgia (PHN). Methods: A total of 103 patients with PHN who were admitted to the Department of Pain Medicine of Henan Provincial People's Hospital from May 2020 to May 2022 were retrospectively selected, including 50 males and 53 females, and aged 40 to 79 (65.4±9.2) years. The patients were divided into two groups according to the treatment methods they received: the control group (n=51) and the study group (n=52). The patients in the control group were treated with oral pregabalin, and the patients in the study group received pregabalin plus high-voltage pulse radiofrequency therapy. The pain intensity and efficacy of the two groups were evaluated before treatment and 4 weeks after treatment. The pain intensity, the sleep quality and the efficacy of treatment was evaluated by visual analogue scale (VAS) score, Pittsburgh Sleep Quality Index (PSQI) score and nimodipine method, respectively. The levels of pain mediators including serum neuropeptide Y (NPY), prostaglandin E2 (PGE2), substance P (SP) and ß-endorphin were measured. The differences of the above indicators and the incidence of adverse reactions were compared between the two groups. Results: The VAS scores of the study group and the control group before treatment were 7.94±0.76 and 8.20±0.81, and PSQI scores were 16.84±3.90 and 16.29±3.84, respectively, with no statistically significant differences (both P>0.05). After 4 weeks of treatment, the VAS scores of the two groups were 2.84±0.80 and 3.35±0.87, and PSQI scores were 6.78±1.90 and 7.98±2.40, respectively, and the VAS score and PSQI score in the study group were lower than those in the control group (both P<0.05). There were no significant differences of the serum levels of NPY, PGE2, SP and ß-endorphin before treatment in the study group and control group (all P>0.05). After 4 weeks of treatment, the levels of NPY, PGE2, SP and ß-Endorphin in the study group were (240.7±26.8) ng/L, (74.4±8.6) µg/L, (108.9±15.7) ng/L and (4.4±0.9) ng/L, which were lower than those in the control group [(268.1±29.4) ng/L, (79.7±8.3) µg/L, (115.2±16.2) ng/L, (5.2±1.3) ng/L, respectively], with statistically significant differences (all P<0.05). After treatment, 29 cases were cured, 16 cases were markedly effective and 6 cases were effective in the study group, while 16 cases, 24 cases and 8 cases were cured, markedly effective and effective in the control group, respectively. The overall efficacy of patients in the study group was better than that in the control group (Z=-2.32, P=0.018). The incidence of adverse reactions in the study group and control group was 11.5% (6/52) and 7.8% (4/51), respectively, with no statistically significant difference (χ2=0.40, P=0.527). Conclusion: High-voltage pulse radiofrequency combined with pregabalin can significantly improve the pain intensity and sleep quality of patients with severe thoracic PHN and reduce the levels of pain mediators, with a high safety profile.

ß-Endorphin (an endogenous opioid) inhibits inflammation, oxidative stress and apoptosis via Nrf-2 in asthmatic murine model.

Asthma, a chronic respiratory disease is characterized by airway inflammation, remodelling, airflow limitation and hyperresponsiveness. At present, it is considered as an umbrella diagnosis consisting several variable clinical presentations (phenotypes) and distinct pathophysiological mechanisms (endotypes). Recent evidence suggests that oxidative stress participates in airway inflammation and remodelling in chronic asthma. Opioids resembled by group of regulatory peptides have proven to act as an immunomodulator. ß-Endorphin a natural and potent endogenous morphine produced in the anterior pituitary gland play role in pain modulation. Therapeutic strategy of many opioids including ß-Endorphin as an anti­inflammatory and antioxidative agent has not been yet explored despite its promising analgesic effects. This is the first study to reveal the role of ß-Endorphin in regulating airway inflammation, cellular apoptosis, and oxidative stress via Nrf-2 in an experimental asthmatic model. Asthma was generated in balb/c mice by sensitizing with 1% Toulene Diisocyanate on day 0, 7, 14 and 21 and challenging with 2.5% Toulene Diisocyanate from day 22 to 51 (on every alternate day) through intranasal route. ß-Endorphin (5 µg/kg) was administered through the nasal route 1 h prior to sensitization and challenge. The effect of ß-Endorphin on pulmonary inflammation and redox status along with parameters of oxidative stress were evaluated. We found that pre-treatment of ß-Endorphin significantly reduced inflammatory infiltration in lung tissue and cell counts in bronchoalveolar lavage fluid. Also, pre-treatment of ß-Endorphin reduced reactive oxygen species, Myeloperoxidase, Nitric Oxide, Protein and protein carbonylation, Glutathione Reductase, Malondialdehyde, IFN-γ, and TNF-α. Reversely, ß-Endorphin significantly increased Superoxide dismutase, Catalase, glutathione, Glutathione-S-Transferase, and activation of NF-E2-related factor 2 (Nrf-2) via Kelch-like ECH-associated protein 1 (Keap1), independent pathway in the lung restoring architectural alveolar and bronchial changes. The present findings reveal the therapeutic potency of ß-END in regulating asthma by Keap-1 independent regulation of Nrf-2 activity. The present findings reveal the therapeutic potency of ß-Endorphin in regulating asthma.

Cell apoptosis in the testis of male rats is elevated by intervention with ß-endorphin and the mu opioid receptor.

ß-endorphin (ß-EP) is involved in the regulation of male germ cells; however, little is known about the effect of ß-EP on primary germ cells via opioid receptors. In this study, we first revealed significant cell apoptosis in the testis of male rats after ß-EP intervention. Subsequently, the expression of the mu opioid receptor (MOR) was detected in both Leydig cells (LCs) and spermatogonia (SGs) by fluorescence colocalization; overlapping signals were also detected in apoptotic cells. In addition, LCs and SGs were separated from the testis of male rats and primary cells were treated with ß-EP; this increased the mRNA levels of MOR and was accompanied by acute cell apoptosis. Our findings provide a foundation for the further study of apoptosis in reproductive cells regulated by ß-EP and the MOR receptor.

[Efficacy and safety of high-voltage pulsed radiofrequency combined with pregabalin on severe thoracic postherpetic neuralgia].

Objective: To investigate the efficacy and safety of high-voltage pulse radiofrequency combined with pregabalin on severe thoracic postherpetic neuralgia (PHN). Methods: A total of 103 patients with PHN who were admitted to the Department of Pain Medicine of Henan Provincial People's Hospital from May 2020 to May 2022 were retrospectively selected, including 50 males and 53 females, and aged 40 to 79 (65.4±9.2) years. The patients were divided into two groups according to the treatment methods they received: the control group (n=51) and the study group (n=52). The patients in the control group were treated with oral pregabalin, and the patients in the study group received pregabalin plus high-voltage pulse radiofrequency therapy. The pain intensity and efficacy of the two groups were evaluated before treatment and 4 weeks after treatment. The pain intensity, the sleep quality and the efficacy of treatment was evaluated by visual analogue scale (VAS) score, Pittsburgh Sleep Quality Index (PSQI) score and nimodipine method, respectively. The levels of pain factors including serum neuropeptide Y (NPY), prostaglandin E2 (PGE2), substance P (SP) and ß-Endorphin were measured. The differences of the above indicators and the incidence of adverse reactions were compared between the two groups. Results: The VAS scores and PSQI scores of the study group and the control group before treatment were (7.94±0.76), (8.20±0.81), (16.84±3.90) and (16.29±3.84), respectively, with no statistically significant difference (both P>0.05). After 4 weeks of treatment, the VAS scores and PSQI scores of the two groups were (2.84±0.80), (3.35±0.87), (6.78±1.90) and (7.98±2.40), respectively, and the VAS score and PSQI score in the study group were lower than those in the control group (both P<0.05). Serum levels of NPY, PGE2, SP and ß-Endorphin were (298.5±31.0) ng/L, (92.3±11.0) µg/L, (156.8±21.4) ng/L, and (8.6±1.6) ng/L in the study group and (304.2±28.6) ng/L, (94.4±12.9) µg/L, (152.7±23.8) ng/L and (8.2±1.8) ng/L in the control group, with no significant differences (all P>0.05). After 4 weeks of treatment, levels of NPY, PGE2, SP and ß-Endorphin were (240.7±26.8) ng/L, (74.4±8.6) µg/L, (108.9±15.7) ng/L and (4.4±0.9) ng/L, which were lower than those in the control group [(268.1±29.4) ng/L, (79.7±8.3) µg/L, (115.2±16.2) ng/L, (5.2±1.3) ng/L, respectively], with statistically significant differences (all P<0.05). After treatment, 29 cases were cured, 16 cases were markedly effective and 6 cases were effective in the study group, while 16 cases, 24 cases and 8 cases were cured, markedly effective and effective in the control group. The overall efficacy of patients in the study group was better than that in the control group (Z=-2.32, P=0.018). The incidence of adverse reactions in the study group and control group was 11.5% (6/52) and 7.8% (4/51), respectively, with no statistically significant difference (χ2=0.40, P=0.527). Conclusion: High-voltage pulse radiofrequency combined with pregabalin can significantly improve the pain and sleep quality of patients with severe thoracic PHN and reduce the level of pain factors, with a high safety profile.

Differences Interval Training and Continuous Training on Endorphin Level and Anxiety Degrees in SECABA Rindam III Siliwangi Student Soldiers with Moderate Anxiety.

Background: Endorphin is a biological change in molecular physiology that is commonly connected with anxiety. An increase in the level of anxiety is caused by both an increase and a decrease in the number of endorphins that are present in the brain; however, up until this point, it has never been reported that there is a relationship between the level of anxiety and the influence of interval training. Objective: The purpose of this study was to analyze the effect of training interval on endorphin level and anxiety degrees of secaba student soldiers with moderate degrees of anxiety. Methods: The subject of the study was a student soldier of Secaba Rindam III Siliwangi with moderate anxiety. The subject of the study gets information about the objectives and procedures of the study. Subjects who are willing to participate in the study sign informed consent. The next step was that group 1 was given an interval training treatment 3 times a week for 12 weeks and group 2 was given continuous training treatment. Results: The results showed that there was a difference where interval training is better than continuous training against increasing endorphin levels (30.9111.733 vs. 39.6519.956; p=0.043). The degree of anxiety decreased significantly after being given interval training treatment (64.64±3.671 vs. 29.50±4.165; p=0.0001). Similarly, there was a significant difference (p=0.027; p<0.05) where the treatment in the interval training group was better than that of the continuous training group against a decrease in the degree of anxiety. Conclusion: Interval training can increase endorphin levels in Secaba Rindam III Siliwangi Student Soldiers with Moderate Anxiety and Interval Training can lower the Degree of Anxiety in Secaba Rindam III Siliwangi Student Soldiers with Moderate Anxiety.

Heme-Induced Macrophage Phenotype Switching and Impaired Endogenous Opioid Homeostasis Correlate with Chronic Widespread Pain in HIV.

Chronic widespread pain (CWP) is associated with a high rate of disability and decreased quality of life in people with HIV-1 (PWH). We previously showed that PWH with CWP have increased hemolysis and elevated plasma levels of cell-free heme, which correlate with low endogenous opioid levels in leukocytes. Further, we demonstrated that cell-free heme impairs ß-endorphin synthesis/release from leukocytes. However, the cellular mechanisms by which heme dampens ß-endorphin production are inconclusive. The current hypothesis is that heme-dependent TLR4 activation and macrophage polarization to the M1 phenotype mediate this phenomenon. Our novel findings showed that PWH with CWP have elevated M1-specific macrophage chemokines (ENA-78, GRO-α, and IP-10) in plasma. In vitro, hemin-induced polarization of M0 and M2 macrophages to the M1 phenotype with low ß-endorphins was mitigated by treating cells with the TLR4 inhibitor, TAK-242. Similarly, in vivo phenylhydrazine hydrochloride (PHZ), an inducer of hemolysis, injected into C57Bl/6 mice increased the M1/M2 cell ratio and reduced ß-endorphin levels. However, treating these animals with the heme-scavenging protein hemopexin (Hx) or TAK-242 reduced the M1/M2 ratio and increased ß-endorphins. Furthermore, Hx attenuated heme-induced mechanical, heat, and cold hypersensitivity, while TAK-242 abrogated hypersensitivity to mechanical and heat stimuli. Overall, these results suggest that heme-mediated TLR4 activation and M1 polarization of macrophages correlate with impaired endogenous opioid homeostasis and hypersensitivity in people with HIV.

Comparative Determination of Natural Antibodies for the Assessment of the Cardiovascular System and the Level of Human Difficulty.

A comparative analysis of natural antibodies to ß-endorphin, angiotensin, dopamine, serotonin, parameters of the cardiovascular system and anxiety levels was carried out for 241 athletes of various qualifications and sports. The obtained indicators of the cardiovascular system were compared with reference values. A significant increase in the level of natural antibodies to angiotensin was established for all groups of athletes. In the case of dopamine, serotonin, these differences are associated with the qualification of the athlete, for ß-endorphin, differences in the level of the indicator depending on the sport were found. A group of individuals with high levels of situational and personal anxiety was found among highly qualified athletes. An increase in blood pressure in athletes of cyclic sports and martial arts is adaptive, and in athletes of speed-strength sports it leads to a change in the walls of the myocardium. As a result of the study, the possibility of a comprehensive determination of natural antibodies and functional indicators as diagnostic markers for assessing the state of the human cardiovascular system has been shown.

Thermochemical Study of the Interaction of Cytosine and Uracil with Peptides in a Buffered Saline: Complex Formation with beta-Endorphin 30-31 (Human), L-Glutathion (Reduced) and α-L-Alanyl-L-Tyrosine.

The complex formation of uracil and cytosine with glycyl-L-glutamic acid (ß-endorphin 30-31), γ-L-glutamyl-L-cysteinyl-glycine (glutathione reduced), α-L-alanyl-L-tyrosine, and α-L-alanyl-α-L-alanine in a buffered saline has been studied using dissolution calorimetry. The values of the reaction constant, the change in Gibbs energy, enthalpy, and entropy were obtained. It is shown that the ratio of the enthalpy and entropy factors depends on the charge of the peptide ion, and the number of H-bond acceptors in the peptide structure. The contributions of interaction between charged groups and polar fragments, hydrogen bonding, and stacking interaction are discussed, taking into account the effect of solvent reorganization around the reactant molecules.

Arsenic exposure and pruritus: Evidence from observational, interventional, and mendelian randomization studies.

BACKGROUND: Pruritus is identified as an adverse drug reaction to arsenic trioxide, but the association of arsenic exposure with pruritus has not been investigated. METHODS: A cross-sectional study was conducted in Shimen, China. A Mendelian randomization analysis was conducted to confirm the causal relationship between genetically predicted percentages of monomethylated arsenic (MMA%) and dimethylated arsenic (DMA%) in urine with chronic pruritus in UK Biobank. A case-control study was then conducted to determine the biomarker for pruritus. Arsenite-treated mice were used to confirm the biomarker, and von Frey test was used to induce scratching bouts. Last, a randomized, double-blind, placebo-controlled trial was conducted to test the efficacy of naloxone in arsenic-exposed patients with pruritus in Shimen. RESULTS: Hair arsenic (µg/g) showed a dose-response relationship with the intensity of itch in 1079 participants, with odds ratios (OR) of 1.11 for moderate-to-severe itch (p = 0.012). The Mendelian randomization analysis confirmed the causal relationship, with ORs of 1.043 for MMA% (p = 0.029) and 0.904 for DMA% (p = 0.077) above versus under median. Serum ß-endorphin was identified as a significant biomarker for the intensity of itch (p < 0.001). Consistently, treatment with arsenite upregulated the level of ß-endorphin (p = 0.002) and induced scratching bouts (p < 0.001) in mice. The randomized controlled trial in 126 participants showed that treatment with sublingual naloxone significantly relieved the intensity of itch in arsenic-exposed participants in 2 weeks (ß = -0.98, p = 0.04). CONCLUSION: Arsenic exposure is associated with pruritus, and ß-endorphin serves as a biomarker of pruritus. Naloxone relieves pruritus in patients with arseniasis.

The effect of delayed umbilical cord clamping on the infant's beta-endorphin level, mother-infant attachment and breastfeeding.

OBJECTIVES: To examine the effect of delayed umbilical cord clamping on the infant's betaendorphin level, mother-infant attachment and breastfeeding. STUDY DESIGN: This study had an experimental design with a control group. The study was undertaken between October and December 2017 in a maternity hospital in the east of Turkey. In total, 107 pregnant women [55 in the experimental group (delayed cord clamping) and 52 in the control group (early cord clamping)] participated in the study. RESULTS: The beta-endorphin level in the umbilical cord was 775.80 ± 229.35 in the experimental group and 547.91 ± 290.01 in the control group, and the difference was significant (t = 4.492, p = 0.000). Similarly, the prolactin level in the umbilical cord was 174.26 ± 47.20 in the experimental group and 119.06 ± 47.74 in the control group, and the difference was significant (t = 6.012, p = 0.000). Mother-infant attachment and breastfeeding success were higher in the experimental group. CONCLUSIONS: Beta-endorphin and prolactin levels in the umbilical cord, mother-infant attachment and breastfeeding success were higher in the group which underwent delayed cord clamping.