-
The European Respiratory Journal May 2023Mucin disulfide cross-links mediate pathologic mucus formation in muco-obstructive lung diseases. MUC-031, a novel thiol-modified carbohydrate compound, cleaves...
BACKGROUND
Mucin disulfide cross-links mediate pathologic mucus formation in muco-obstructive lung diseases. MUC-031, a novel thiol-modified carbohydrate compound, cleaves disulfides to cause mucolysis. The aim of this study was to determine the mucolytic and therapeutic effects of MUC-031 in sputum from patients with cystic fibrosis (CF) and mice with muco-obstructive lung disease (βENaC-Tg mice).
METHODS
We compared the mucolytic efficacy of MUC-031 and existing mucolytics (N-acetylcysteine (NAC) and recombinant human deoxyribonuclease I (rhDNase)) using rheology to measure the elastic modulus (G') of CF sputum, and we tested effects of MUC-031 on airway mucus plugging, inflammation and survival in βENaC-Tg mice to determine its mucolytic efficacy .
RESULTS
In CF sputum, compared to the effects of rhDNase and NAC, MUC-031 caused a larger decrease in sputum G', was faster in decreasing sputum G' by 50% and caused mucolysis of a larger proportion of sputum samples within 15 min of drug addition. Compared to vehicle control, three treatments with MUC-031 in 1 day in adult βENaC-Tg mice decreased airway mucus content (16.8±3.2 7.5±1.2 nL·mm, p<0.01) and bronchoalveolar lavage cells (73 833±6930 47 679±7736 cells·mL, p<0.05). Twice-daily treatment with MUC-031 for 2 weeks also caused decreases in these outcomes in adult and neonatal βENaC-Tg mice and reduced mortality from 37% in vehicle-treated βENaC-Tg neonates to 21% in those treated with MUC-031 (p<0.05).
CONCLUSION
MUC-031 is a potent and fast-acting mucolytic that decreases airway mucus plugging, lessens airway inflammation and improves survival in βENaC-Tg mice. These data provide rationale for human trials of MUC-031 in muco-obstructive lung diseases.
Topics: Adult; Humans; Mice; Animals; Expectorants; Sulfhydryl Compounds; Cystic Fibrosis; Acetylcysteine; Sputum; Lung Diseases, Obstructive; Inflammation; Carbohydrates; Lung
PubMed: 37080569
DOI: 10.1183/13993003.02022-2022 -
Advanced Healthcare Materials Sep 2023Intervertebral disc degeneration (IVDD) is associated with oxidative stress induced reactive oxygen species (ROS) dynamic equilibrium disturbance. Nanozymes, as...
Intervertebral disc degeneration (IVDD) is associated with oxidative stress induced reactive oxygen species (ROS) dynamic equilibrium disturbance. Nanozymes, as nanomaterials with enzyme-like activity, can regulate intro-cellular ROS levels. In this study, a new carbon dots nanozyme, N-acetylcysteine-derived carbon dots (NAC-CDs), is developed and proved to be an ideal antioxidant and anti-senescent agent in IVDD management. The results confirmed the NAC-CDs have satisfactory biocompatibility and strong superoxide dismutase (250 U mg ), catalase, glutathioneperoxidase-like activity, and total antioxidant capacity. Then, the powerful free radical scavenging and antioxidant ability of NAC-CDs are demonstrated in vitro as observing the reduced ROS in H O induced senescent nucleus pulposus cells (NPCs), in which the elimination efficiency of toxic ROS is more than 90%. NAC-CDs also maintained mitochondrial homeostasis and suppressed cellular senescence, subsequently inhibited the expression of inflammatory factors in NPCs. In vivo, evaluations of imaging and tissue morphology assessments suggested that disc height index, magnetic resonance imaging grade and histological score are significantly improved from the degenerative models when NAC-CDs is applied. In conclusion, the study developed a novel carbon dots nanozyme, which efficiently rescues IVDD from ROS induced NPCs senescence and provides a potential strategy in management of IVDD in clinic.
Topics: Humans; Intervertebral Disc Degeneration; Acetylcysteine; Antioxidants; Reactive Oxygen Species; Nucleus Pulposus
PubMed: 37256605
DOI: 10.1002/adhm.202300533 -
Italian Journal of Pediatrics Jul 2023To examine the clinical impact of bronchoscope alveolar lavage (BAL) combination with budesonide, ambroxol + budesonide, or acetylcysteine + budesonide in the...
BACKGROUND
To examine the clinical impact of bronchoscope alveolar lavage (BAL) combination with budesonide, ambroxol + budesonide, or acetylcysteine + budesonide in the treatment of refractory Mycoplasma pneumoniae pneumonia (RMPP).
METHODS
Eighty-two RMPP patients admitted to Pediatrics at The First People's Hospital of Zhengzhou were retrospectively evaluated between August 2016 and August 2019. All patients were administered BAL in addition to intravenous Azithromycin, expectoration, and nebulizer inhalation. The medications added to the BLA separated the patients into the Budesonide group, Ambroxol + budesonide group, and acetylcysteine + budesonide group. Analyzed were the variations in laboratory examination indices, improvement in lung imaging, overall effective rate, and adverse responses in the three groups.
RESULTS
The laboratory test indices of patients in all three groups improved significantly relative to pre-treatment levels, and the results were statistically significant. After therapy, there were no significant differences between the three groups in terms of white blood cell (WBC), C-reactive protein (CRP), or erythrocyte sedimentation rate (ESR). Serum lactate dehydrogenase (LDH) and serum ferritin (SF) varied significantly across the three groups (P < 0.05). In the acetylcysteine + budesonide group, the absorption rate of lung imaging lesions and clinical efficacy were superior to those of the other two groups. There were no significant differences between the three groups in the occurrence of adverse events (P > 0.05).
CONCLUSIONS
BLA-coupled acetylcysteine + budesonide was superior to the other two groups in enhancing the effectiveness of RMPP in children, which might increase lung opacity absorption and minimize lung inflammation.
Topics: Child; Humans; Mycoplasma pneumoniae; Acetylcysteine; Retrospective Studies; Budesonide; Ambroxol; Pneumonia, Mycoplasma
PubMed: 37422684
DOI: 10.1186/s13052-023-01491-y -
Neuropsychopharmacology : Official... Jul 2023Current treatments for adolescent alcohol use disorder (AUD) are mainly psychosocial and limited in their efficacy. As such, pharmacotherapies are being investigated as... (Randomized Controlled Trial)
Randomized Controlled Trial
Current treatments for adolescent alcohol use disorder (AUD) are mainly psychosocial and limited in their efficacy. As such, pharmacotherapies are being investigated as potential adjunctive treatments to bolster treatment outcomes. N-acetylcysteine is a promising candidate pharmacotherapy for adolescent AUD because of its tolerability and demonstrated ability to modulate glutamatergic, GABAergic, and glutathione systems. The primary objective of this double-blind, placebo-controlled, within-subjects crossover preliminary investigation was to measure potential changes within glutamate + glutamine (Glx), GABA, and glutathione levels in the dorsal anterior cingulate cortex (dACC) using proton magnetic resonance spectroscopy during 10-days of N-acetylcysteine (1200 mg twice daily) compared to 10-days of placebo in non-treatment seeking adolescents who use alcohol heavily (N = 31; 55% female). Medication adherence was confirmed via video. Effects on alcohol use were measured using Timeline Follow-Back as an exploratory aim. Linear mixed effects models controlling for baseline metabolite levels, brain tissue composition, alcohol use, cannabis use, and medication adherence found no significant differences in Glx, GABA, or glutathione levels in the dACC after N-acetylcysteine compared to placebo. There were also no measurable effects on alcohol use; however, this finding was underpowered. Findings were consistent in the subsample of participants who met criteria for AUD (n = 19). The preliminary null findings in brain metabolite levels may be due to the young age of participants, relatively low severity of alcohol use, and non-treatment seeking status of the population investigated. Future studies can use these findings to conduct larger, well-powered studies within adolescents with AUD.
Topics: Humans; Adolescent; Female; Male; Acetylcysteine; Alcoholism; Alcohol Drinking; Ethanol; Double-Blind Method; Glutathione; gamma-Aminobutyric Acid; Glutamic Acid
PubMed: 36878996
DOI: 10.1038/s41386-023-01553-z -
Ulusal Travma Ve Acil Cerrahi Dergisi =... Jan 2021In burn wound healing, zones of burn, namely zone of hyperemia, the zone of stasis, and zone of coagulation, have crucial importance. These zones have been identified...
BACKGROUND
In burn wound healing, zones of burn, namely zone of hyperemia, the zone of stasis, and zone of coagulation, have crucial importance. These zones have been identified based on the pathophysiology of the burn, and treatment of burn has been improved. The zone of necrosis is treated by excision and repair through grafting. Zone of stasis fully recovers in 24-48 h if the burn treatment is managed well. Otherwise, it may convert to a zone of coagulation. Hyperemia zone is a zone that recovers itself. Recovery of the zone of stasis is very critical in burn treatment. Active oxygen radicals produced due to the hypermetabolism due to burn wounds are known to speed to the process of the zone of stasis converting into the zone of coagulation. The present experimental study aims to evaluate the effects of sildenafil and N-acetylcysteine on the zone of stasis and to establish whether they had any contribution to wound healing in burns.
METHODS
In the present study, 32 four months old female Wistar Albino rats with 200±20 gr body weights were used. The rats were divided into four groups as the sham group (Group 1), the intraperitoneal group (Group 2), Sildenafil group (Group 3, intraperitoneal 10 mg/kg for 10 days), N-acetylcysteine (Group 4, intraperitoneal 100 mg/kg for 10 days). Tissue samples were collected for serum and cytopathology studies of the Malondialdehyde level, glutathione peroxidase, superoxide dismutase, and catalyze enzyme activity. All the rats were sacrificed on the 10th day of the tests edema, hyperemia, epithelial degeneration, necrosis, inflammatory infiltration and fibrosis measurements were made.
RESULTS
When compared with the controls, both of the treatment groups had lower tissue damage scores. MDA level was lower in Group 3 and 4 compared to Group 2 and lower in Group 3 compared to Group 4. SOD, catalase and GPH-Px levels were higher in Group 3 and Group 4 compared to Group 2 and higher in Group 3 compared to Group 4.
CONCLUSION
The results of our study conducted on an experimental burn model created by rats support that Sildenafil and N-acetylcysteine have positive effects, such as decreasing oxidative stress level and increasing wound healing in burns. Further experimental studies are required on this subject.
Topics: Acetylcysteine; Animals; Burns; Female; Oxidative Stress; Rats; Rats, Wistar; Sildenafil Citrate; Wound Healing
PubMed: 33394467
DOI: 10.14744/tjtes.2020.25679 -
Cellular Microbiology Feb 2021Viruses confiscate cellular components of the ubiquitin-proteasome system (UPS) to facilitate many aspects of the infectious cycle. The 26S proteasome is an... (Review)
Review
Viruses confiscate cellular components of the ubiquitin-proteasome system (UPS) to facilitate many aspects of the infectious cycle. The 26S proteasome is an ATP-dependent, multisubunit proteolytic machine present in all eukaryotic cells. The proteasome executes the controlled degradation of functional proteins, as well as the hydrolysis of aberrantly folded polypeptides. There is growing evidence for the role of the UPS in viral entry. The UPS assists in several steps of the initiation of infection, including endosomal escape of the entering virion, intracellular transport of incoming nucleocapsids and uncoating of the viral genome. Inhibitors of proteasome activity, including MG132, epoxomicin, lactacystin and bortezomib have been integral to developments in this area. Here, we review the mechanistic details of UPS involvement in the entry process of viruses from a multitude of families. The possibility of proteasome inhibitors as therapeutic antiviral agents is highlighted.
Topics: Acetylcysteine; Animals; Antiviral Agents; Bortezomib; Host Microbial Interactions; Humans; Leupeptins; Nucleocapsid; Oligopeptides; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Proteolysis; Ubiquitin; Virion; Virus Internalization; Virus Physiological Phenomena; Viruses
PubMed: 33037857
DOI: 10.1111/cmi.13276 -
Survey of Ophthalmology 2022N-acetylcysteine (NAC) was first discovered as a mucolytic agent in 1960. We investigate the role of topical NAC in ocular therapeutics, including its mechanism of... (Review)
Review
N-acetylcysteine (NAC) was first discovered as a mucolytic agent in 1960. We investigate the role of topical NAC in ocular therapeutics, including its mechanism of action, current applications, and adverse effects. A systematic search of peer-reviewed articles identified 106 references including in vitro, in vivo and clinical studies on the use of NAC in the treatment of ocular diseases. NAC can be synthetically manufactured, and its mechanisms of action include mucolysis, scavenging hydroxyl radicals, and modulation of inflammatory cascades. These unique properties contribute to the diverse applications of NAC, including its steroid-sparing potential. NAC has been used topically in the treatment of corneal wounds, chemical injuries, keratitis, dry eye disease and meibomian gland dysfunction. The clinical benefits of NAC are evident over a wide range of concentrations, the most common being 5-10% topical NAC applied four times daily. Adverse effects such as corneal necrosis are rare, but have been reported with higher doses. NAC also has potential applications in laser epithelial keratomileusis, diabetic eye disease, retinitis pigmentosa, senile nuclear cataracts, macular degeneration, and cigarette smoke-induced corneal damage. Recently, chitosan-NAC has been used as a nanocarrier for the topical administration of medications to the ocular surface. Owing to its potent antioxidant, anti-inflammatory and mucolytic properties, topical NAC has had extensive use in the treatment of ocular pathology.
Topics: Acetylcysteine; Administration, Topical; Chitosan; Cornea; Dry Eye Syndromes; Humans
PubMed: 34339721
DOI: 10.1016/j.survophthal.2021.07.008 -
Contemporary Clinical Trials Aug 2023Tobacco and cannabis co-use is a growing public health problem. The synergistic effects of cannabis and nicotine on neurobiological systems that mediate reward and...
BACKGROUND
Tobacco and cannabis co-use is a growing public health problem. The synergistic effects of cannabis and nicotine on neurobiological systems that mediate reward and shared environmental cues reinforcing use may make tobacco smoking cessation more difficult. N-acetylcysteine (NAC), an FDA-approved medication and over-the-counter supplement, has shown promise in animal studies and randomized controlled trials (RCTs) in reducing tobacco and cannabis craving and use. NAC's potential efficacy in treating addiction may be attributable to its central nervous system effects in reducing excessive glutamatergic activity, oxidative stress, and inflammation. To date, no RCT has examined NAC for smoking cessation among dual users of tobacco and cannabis.
METHOD
In a double-blind, placebo-controlled RCT, we will examine NAC for smoking cessation among dual users of tobacco and cannabis. Sixty adult cigarette-cannabis co-users are randomized to receive NAC 3600 mg per day or placebo over 8 weeks. Participants in both groups receive 8 weekly cognitive behavioral therapy sessions addressing smoking cessation and cannabis reduction. Outcomes are assessed at Weeks 0, 4, 8, and 12. Primary aims are to determine NAC's efficacy in decreasing cigarette craving, nicotine dependence, and use; and cannabis craving and use. Exploratory aims include examination of changes in neurocognition with NAC and their potential mediational effects on cigarette and cannabis use outcomes.
CONCLUSION
Results will inform smoking cessation treatment among dual users of tobacco and cannabis.
CLINICALTRIALS
gov Identifier: NCT04627922.
Topics: Adult; Humans; Smoking Cessation; Cannabis; Acetylcysteine; Tobacco Use Disorder; Randomized Controlled Trials as Topic
PubMed: 37271412
DOI: 10.1016/j.cct.2023.107250 -
Nutrients May 2023Administering N-acetylcysteine (NAC) could counteract the effect of free radicals, improving the clinical evolution of patients admitted to the Intensive Care Unit... (Randomized Controlled Trial)
Randomized Controlled Trial
Administering N-acetylcysteine (NAC) could counteract the effect of free radicals, improving the clinical evolution of patients admitted to the Intensive Care Unit (ICU). This study aimed to investigate the clinical and biochemical effects of administering NAC to critically ill patients with COVID-19. A randomized controlled clinical trial was conducted on ICU patients ( 140) with COVID-19 and divided into two groups: patients treated with NAC (NAC-treated group) and patients without NAC treatment (control group). NAC was administered as a continuous infusion with a loading dose and a maintenance dose during the study period (from admission until the third day of ICU stay). NAC-treated patients showed higher PaO/FiO ( 0.014) after 3 days in ICU than their control group counterparts. Moreover, C-reactive protein ( 0.001), D-dimer ( 0.042), and lactate dehydrogenase ( 0.001) levels decreased on the third day in NAC-treated patients. Glutathione concentrations decreased in both NAC-treated ( 0.004) and control ( 0.047) groups after 3 days in ICU; whereas glutathione peroxidase did not change during the ICU stay. The administration of NAC manages to improve the clinical and analytical response of seriously ill patients with COVID-19 compared to the control group. NAC is able to stop the decrease in glutathione concentrations.
Topics: Humans; Acetylcysteine; COVID-19; Critical Illness; Glutathione; Dietary Supplements
PubMed: 37405379
DOI: 10.3390/nu15092235 -
Human Psychopharmacology Mar 2024N-acetylcysteine (NAC) augmentation of antipsychotic medication has been studied in psychotic disorders but the results are inconsistent. This meta-analysis aimed to... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
N-acetylcysteine (NAC) augmentation of antipsychotic medication has been studied in psychotic disorders but the results are inconsistent. This meta-analysis aimed to evaluate the efficacy and acceptability of NAC as an augmentation strategy for psychotic disorders.
METHODS
PubMed, Web of Science, EMBASE, PsycINFO, Cochrane Library, and ClinicalTrials.gov were searched until the date of November 28, 2022. The inclusion criteria were randomized controlled trials (RCTs) comparing NAC and placebo in patients with psychotic disorders. The outcomes were the psychotic symptoms measured by the Positive and Negative Syndrome Scale (PANSS) and drop-out rates.
RESULTS
A total of 594 patients from eight trials were included. The results showed that no difference was found in score changes of PANSS total, positive, negative, or general psychopathology scale scores between the NAC group and placebo group in both time points (≤24 weeks and >24 weeks). There was also no statistical difference in drop-out rates between the two groups.
CONCLUSION
For the moment, it is not appropriate to recommend NAC as an augmentation of antipsychotic medication to treat psychotic disorders in routine clinical practice.
Topics: Humans; Acetylcysteine; Antipsychotic Agents; Schizophrenia; Psychotic Disorders; Randomized Controlled Trials as Topic
PubMed: 37712506
DOI: 10.1002/hup.2880