This study aimed to explore the roles of microRNAs (miRNAs) in the post-transcriptional regulation of cocaine- and amphetamine-regulated transcript (CART) peptide in the bovine hypothalamus and to screen key regulatory miRNAs. Targetscan was used to predict the potential miRNAs binding to CART 3' untranslated regions (3'UTR). Bioinformatics analysis predicted 7 miRNA binding sites in the bovine CART 3'UTR, which were bta-miR-377, bta-miR-331-3p, bta-miR-491, bta-miR-493, bta-miR-758, bta-miR-877, and bta-miR-381, respectively. Reverse transcription-PCR (RT-PCR) was carried out to determine the endogenous expression of CART and target miRNAs in the bovine hypothalamus. All the 7 target miRNAs and CART were endogenously expressed in the bovine hypothalamus. The dual-luciferase reporter gene assay was employed to detect the targeted binding relationship between CART 3'UTR and target miRNAs obtained from bioinformatics analysis. The dual-luciferase reporter gene assay confirmed that the 3'UTR of CART had a targeted binding relationship with the 7 target miRNAs. Cell experiments were conducted to examine the effects of target miRNAs on the messenger RNA (mRNA) and protein levels of exogenous CART and screen for key regulatory miRNAs. The results of cell experiments showed that the 7 miRNAs downregulated the mRNA level of CART, with bta-miR-491 demonstrating the strongest downregulating effect. Bta-miR-377, bta-miR-331-3p, bta-miR-491, bta-miR-493, and bta-miR-381 downregulated the protein level of CART, with bta-miR-381 exerting the strongest downregulating effect. Animal experiments were conducted to explore the effects of key regulatory miRNAs on the mRNA and protein levels of CART in the hypothalamus and the CART concentration in the serum. The results from animal experiments showed that miR-491 and miR-381 regulated the endogenous expression of CART in the hypothalamus and the concentration in the serum by binding to the CART 3'UTR. These results suggest that miR-491 and miR-381 are the main miRNAs regulating CART expression in the bovine hypothalamus, which can affect serum CART concentration by modulating endogenous CART expression.
Animals ; MicroRNAs/metabolism* ; Cattle ; Hypothalamus/metabolism* ; 3' Untranslated Regions/genetics* ; Nerve Tissue Proteins/metabolism* ; Gene Expression Regulation ; Binding Sites ; Base Sequence ; Computational Biology/methods* ; Cocaine- and Amphetamine-Regulated Transcript Protein

Objective: To investigate the effect of sugammadex on postoperative nausea and vomiting(PONV) after intracranial aneurysm surgery. Methods: Data from intracranial aneurysms patients who met the inclusion and exclusion criteria and underwent interventional surgery in the Department of Neurosurgery, Peking University International Hospital from January 2020 to March 2021 were prospectively included. According to the random number table method, the patients were divided by 1∶1 into the neostigmine+atropine group (group N) and the sugammadex group (group S). Use an acceleration muscle relaxation monitor for muscle relaxation monitoring, and administer neostigmine+atropine and sugammadex to block residual muscle relaxation drugs after surgery. The incidence rates of PONV and severity, the appearance of anesthesia, and the correlation between PONV and postoperative complications were recorded in both groups during five periods after surgery: 0-0.5 hours (T1),>0.5-2.0 hours(T2),>2.0-6.0 hours (T3),>6.0-12.0 hours (T4) and >12.0-24.0 hours (T5). Group comparisons of quantitative data were performed by the independent sample t-test, and categorical data was performed by the χ² or rank sum test. Results: A total of 66 patients were included in the study, including 37 males and 29 female, aged (59.3±15.4) years (range: 18 to 77 years). The incidence rates of PONV of 33 patients in group S at different time periods of T1, T2, T3, T4, and T5 after surgery were respectively 27.3%(9/33),30.3%(10/33),12.1%(4/33),3.0%(1/33),0(0/33),and the incidence rates of PONV of 33 patients in the group N at different time periods of T1, T2, T3, T4 and T5 after surgery were respectively 36.4%(12/33),36.4%(12/33),33.3%(11/33),6.1%(2/33) and 0(0/33).The incidence of PONV was lower in the group S only in the T3 period after reversal than in the group N (χ²=4.227, P=0.040).However, there was no statistically significant difference in the incidence of PONV between the two groups of patients in other periods (all P>0.05). The recovery time for spontaneous breathing in patients in group S was (7.7±1.4) minutes, the extubation time was (12.4±5.3) minutes, and the safe exit time for anesthesia recovery was (12.3±3.4) minutes; the N groups were (13.9±2.0) minutes, (18.2±6.0) minutes, and (18.6±5.2) minutes, respectively; three time periods in group S were shorter than those in group N, and the differences were statistically significant (all P<0.05). The results regarding the occurrence of complications in patients with different levels of PONV at different time intervals after surgery in the two groups were as follows: in the T3 time period of group N, a significant difference was observed only in the occurrence of postoperative complications among patients with different levels of PONV (χ²=24.786, P<0.01). However, in the T4 time period, significant differences were found in the occurrence of postoperative complications among both the same level and different level PONV patients (χ²=15.435, 15.435, both P<0.01). Significant differences were also observed in the occurrence of postoperative complications among the same level and different level PONV patients in both the T3 and T4 time periods of group S (all P<0.01). Conclusion: Sugammadex can be used to reverse muscle relaxation in patients undergoing intracranial aneurysm intervention surgery,and it does not have a significant impact on the incidence of PONV, it can also optimize the quality of anesthesia recovery and reduce the incidence of complications after intracranial aneurysm embolization surgery.
Male ; Humans ; Female ; Sugammadex ; Postoperative Nausea and Vomiting/chemically induced* ; Neostigmine/adverse effects* ; Intracranial Aneurysm/surgery* ; gamma-Cyclodextrins/adverse effects* ; Atropine

Drug-associated reward memories are conducive to intense craving and often trigger relapse. Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is elusive. Here, we used a mass spectrometry-based lipidomic method to evaluate the impact of simvastatin on the mouse brain in a cocaine-induced reinstatement paradigm. We found that simvastatin blocked the reinstatement of cocaine-induced conditioned place preference (CPP) without affecting CPP acquisition. Specifically, only simvastatin administered during extinction prevented cocaine-primed reinstatement. Global lipidome analysis showed that the nucleus accumbens was the region with the greatest degree of change caused by simvastatin. The metabolism of fatty-acids, phospholipids, and triacylglycerol was profoundly affected. Simvastatin reversed most of the effects on phospholipids induced by cocaine. The correlation matrix showed that cocaine and simvastatin significantly reshaped the lipid metabolic pathways in specific brain regions. Furthermore, simvastatin almost reversed all changes in the fatty acyl profile and unsaturation caused by cocaine. In summary, pre-extinction treatment with simvastatin facilitates cocaine extinction and prevents cocaine relapse with brain lipidome remodeling.
Animals ; Brain ; Cocaine ; Conditioning, Operant ; Extinction, Psychological ; Lipidomics ; Male ; Mice ; Simvastatin/therapeutic use*

The Solanaceae plants distributed in China belong to 105 species and 35 varietas of 24 genera. Some medicinal plants of Solanaceae are rich in tropane alkaloids(TAs), which have significant pharmacological activities. In this paper, the geographical distribution, chemical components, traditional therapeutic effect, pharmacological activities, and biosynthetic pathways of TAs in Solanaceous plants were summarized. Besides, the phylogeny of medicinal plants belonging to Solanaceae was visualized by network diagram. Fourteen genera of Solanaceae plants in China contain TAs and have medical records. TAs mainly exist in Datura, Anisodus, Atropa, Physochlaina, and Hyoscyamus. The TAs-containing species were mainly concentrated in Southwest China, and the content of TAs was closely related to plant distribution area and altitude. The Solanaceae plants containing TAs mainly have antispasmodic, analgesic, antiasthmatic, and antitussive effects. Modern pharmacological studies have proved the central sedative, pupil dilating, glandular secretion-inhibiting, and anti-asthma activities of TAs. These pharmacological activities provide a reasonable explanation for the traditional therapeutic efficacy of tropane drugs. In this paper, the geographical distribution, chemical components, traditional therapeutic effect, and modern pharmacological activities of TAs-containing species in Solanaceae were analyzed for the first time. Based on these data, the genetic relationship of TAs-containing Solanaceae species was preliminarily discussed, which provided a scientific basis for the basic research on TAs-containing solanaceous species and was of great significance for the development of natural medicinal plant resources containing TAs.
Biosynthetic Pathways ; Phylogeny ; Plants, Medicinal ; Solanaceae/genetics* ; Tropanes

Drug addiction is a major worldwide medical and social problem.Cocaine,nicotine,methamphetamine,heroin and other psychoactive substances,with small molecular weight,can easily cross the blood-brain barrier and eventually lead to addiction and other serious neuropsychological damage.There is no effective cure for addiction currently.The drug-antibody complex formed on the basis of active or passive immunotherapy could not cross the blood-brain barrier,which reduces the concentration of the free active drug and prevents its distribution in the brain,thereby weakening the drug addiction-related reward effects.It provides a promising way for the treatment of drug addiction.This article reviews the progress of immunotherapy against psychoactive substances such as cocaine,nicotine,methamphetamine and heroin in the past 50 years from the aspects of active immunity,passive immunity,drug metabolism-related enzymes,adjuvants and so on.The goal is to provide some ideas for the development of agents for the treatment of psychoactive substance addiction.
Cocaine ; Humans ; Immunotherapy ; Methamphetamine ; Nicotine ; Substance-Related Disorders/therapy*

PURPOSE: We report a case of Urrets-Zavalia syndrome with a fixed dilated pupil after an uneventful trabeculectomy.CASE SUMMARY: Trabeculectomy was performed on a 51-year-old male who had a history of recurrent uveitis in the left eye, with uncontrolled intraocular pressure despite maximally-tolerated medial therapy. There was no unexpected event during surgery. Topical 1% atropine was used for only 2 days after surgery. In the early postoperative period, 1% prednisolone and 0.3% ofloxacin were given four times a day, then gradually reduced. One month later, only 1% prednisolone was given once a day. Intraocular pressure in his left eye was well controlled from 8–14 mmHg after surgery. One month after surgery, the pupils remained dilated. There was no reaction to topical 2% pilocarpine and no relative afferent pupillary defect or posterior synechia.CONCLUSIONS: Our case, although rare, suggests that Urrets-Zavalia syndrome should be considered in patients with well-controlled intraocular pressure after uneventful trabeculectomy.
Atropine ; Humans ; Intraocular Pressure ; Male ; Middle Aged ; Ofloxacin ; Pilocarpine ; Postoperative Period ; Prednisolone ; Pupil ; Pupil Disorders ; Trabeculectomy ; Uveitis

Atropa belladonna seedlings were used as experimental materials and cultivated by soil culture method. Different concentrations(0,0.05,0.1,0.2,0.5 mmol·L~(-1))of NO donor sodium nitroprusside(SNP) were sprayed on the leaves. The effects of different concentrations of SNP and different treatment time(4,8,12,16 d) on nitrogen metabolism, secondary metabolite content, precursor content of tropane alkaloid synthesis pathway and expression of key enzyme genes under 100 mmol·L~(-1) NaCl stress were studied. The results showed that with the prolongation of salt stress, the nitrogen metabolism and the accumulation of secondary metabolites of A. belladonna were inhibited to some extent. After treatment with different concentrations of exogenous SNP, the ammonium nitrogen content decreased dramatically, and the contents of nitrate nitrogen, free amino acid, soluble protein and the activities of key enzymes of nitrogen metabolism(NR, GS, GDH) were all greatly improved; the contents of precursor amino acids(ornithine, arginine) and polyamines(Put, Spd, Spm) in the secondary metabolic pathway have increased to varying degrees. The qRT-PCR analysis showed that exogenous SNP treatment can effectively promote the high expression of key enzyme genes PMT, TRⅠ and H6H in the secondary metabolic pathway of A. belladonna, and the production of hyoscyamine and scopolamine were increased notably. In summary, the application of appropriate concentration of SNP can effectively alleviate the inhibition of salt stress on the nitrogen metabolism and secondary metabolism of Atropa belladonna, and enhance its salt tolerance. Overall, 0.1 mmol·L~(-1) and 0.2 mmol·L~(-1) SNP treatment achieved the most remarkable effect.
Atropa belladonna/metabolism* ; Hyoscyamine/analysis* ; Nitrogen/metabolism* ; Nitroprusside ; Scopolamine/analysis* ; Secondary Metabolism ; Sodium Chloride ; Stress, Physiological

Cardiovascular and central nervous system (CNS) toxicity, including tachydysrhythmia, agitation, and seizures, may arise from cocaine or bupropion use. We report acute toxicity from the concomitant use of cocaine and bupropion in a 25-year-old female. She arrived agitated and uncooperative, with a history of possible antecedent cocaine use. Her electrocardiogram demonstrated tachycardia at 130 beats/min, with a corrected QT interval of 579 ms. Two doses of 5 mg intravenous metoprolol were administered, which resolved the agitation, tachydysrhythmia, and corrected QT interval prolongation. Her comprehensive toxicology screen returned positive for both cocaine and bupropion. We believe clinicians should be aware of the potential for synergistic cardiovascular and CNS toxicity from concomitant cocaine and bupropion use. Metoprolol may represent an effective initial treatment. Unlike benzodiazepines, metoprolol directly counters the pharmacologic effects of stimulants without respiratory depression, sedation, or paradoxical agitation. A lipophilic beta-blocker, metoprolol has good penetration of the CNS and can counter stimulant-induced agitation.
Adult ; Benzodiazepines ; Bupropion ; Central Nervous System ; Cocaine ; Dihydroergotamine ; Electrocardiography ; Female ; Humans ; Metoprolol ; Respiratory Insufficiency ; Seizures ; Tachycardia ; Toxicology

BACKGROUND: New complications associated with sugammadex have been increased since its widespread use. We report a case of an 80-year-old male who experienced profound bradycardia and sustained hypotension after administration of sugammadex. CASE: Following administration of 200 mg sugammadex after laparoscopic cholecystectomy, sudden bradycardia (29 beats/min) developed for 10 seconds and his train-of-four (TOF) ratio remained at 0.2 for 5 min. An additional 200 mg sugammadex was administered and profound bradycardia (21–30 beats/min) and hypotension (60/40 mmHg) developed. Atropine at 0.5 mg was administered, but the effect lasted only 30 s. Profound bradycardia occurred four more times at 30 s intervals, and ephedrine and phenylephrine were injected intermittently to increase the patient's heart rate and blood pressure. The TOF ratio became 0.9 about 10 min after administration of additional sugammadex. CONCLUSIONS: Awareness must be heightened regarding the possibility of sugammadexinduced bradycardia and hypotension, and more attention should be paid to patients with slow recovery times following muscle relaxation, despite the use of sugammadex.
Aged, 80 and over ; Atropine ; Blood Pressure ; Bradycardia ; Cholecystectomy, Laparoscopic ; Ephedrine ; Heart Rate ; Humans ; Hypotension ; Male ; Muscle Relaxation ; Neuromuscular Blockade ; Phenylephrine ; Postoperative Complications

BACKGROUND: The trigeminocardiac reflex (TCR), which occurs after stimulation of the territory of the trigeminal nerve, is very rarely reported to be caused by stimulation of the mandibular branch. We report a case of TCR in open reduction for temporomandibular joint (TMJ) dislocation. CASE: A 74-year-old female presented for TMJ dislocation. During open reduction of TMJ under general anesthesia, severe bradycardia (15 beats/min) occurred. Immediately 0.5 mg atropine was administered intravenously, and the surgical manipulation was stopped. After 30 seconds, heart rate normalized. During surgery, severe bradycardia occurred one more time. It disappeared spontaneously as soon as surgical manipulation was stopped. The surgery was completed uneventfully. CONCLUSIONS: Because of the possibility of profound bradycardia, asystole, or even death when evoked, it is important to be aware of the trigeminocardiac reflex during manipulation of the mandibular divisions, especially during surgical stimulation of the TMJ.
Aged ; Anesthesia, General ; Atropine ; Bradycardia ; Dislocations ; Female ; Heart Arrest ; Heart Rate ; Humans ; Reflex, Trigeminocardiac ; Temporomandibular Joint ; Trigeminal Nerve