Cardiovascular disease remains the leading cause of death in China, with its morbidity and mortality continue to rise. Ferroptosis, a unique form of iron-dependent cell death, plays a major role in many heart diseases. The classical mechanisms of ferroptosis include iron metabolism disorder, oxidative antioxidant imbalance and lipid peroxidation. Recent studies have found many additional mechanisms of ferroptosis, such as coenzyme Q10, ferritinophagy, lipid autophagy, mitochondrial metabolism disorder, and the regulation by nuclear factor erythroid 2-related factor 2 (NRF2). This article reviews recent advances in understanding the mechanisms of ferroptosis and its role in heart failure, myocardial ischemia/reperfusion injury, diabetic cardiomyopathy, myocardial toxicity of doxorubicin, septic cardiomyopathy, and arrhythmia. Furthermore, we discuss the potential of ferroptosis inhibitors/inducers as therapeutic targets for heart diseases, suggesting that ferroptosis may be an important intervention target of heart diseases.
Ferroptosis/physiology* ; Humans ; Heart Diseases/physiopathology* ; NF-E2-Related Factor 2/physiology* ; Animals ; Myocardial Reperfusion Injury/physiopathology* ; Lipid Peroxidation ; Heart Failure/physiopathology* ; Iron/metabolism* ; Diabetic Cardiomyopathies/physiopathology* ; Ubiquinone/analogs & derivatives*

The aim of this study is to investigate the protective effect of idebenone (IDE) combined with borneol (BO) against Parkinson's disease (PD). In this study, wild-type AB zebrafish and transgenic Tg ( vmat2: GFP) zebrafish with green fluorescence labeled dopamine neurons were used to establish the PD model with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP). Following drug treatment, the behavioral performance and dopamine neuron morphology of zebrafish were evaluated, and regulation of dopamine signaling pathway-related genes was determined using RT-qPCR. The results showed that IDE combined with BO improved the behavioral disorders of zebrafish such as bradykinesia and shortening movement distance, also effectively reversed the damage of MPTP-induced dopaminergic neurons. At the same time, the expression of dopamine synthesis and transportation-related genes was up-regulated, and the normal function of the signal transduction pathway was restored. The combination showed a better therapeutic effect compared to the IDE monotherapy group. This study reveals the protective mechanism of IDE combined with BO on the central nervous system for the first time, which provides an important experimental basis and theoretical reference for clinical combination strategy in PD treatment.
Animals ; Zebrafish ; Signal Transduction/drug effects* ; Animals, Genetically Modified ; Dopamine/metabolism* ; Neuroprotective Agents/pharmacology* ; Disease Models, Animal ; Camphanes/pharmacology* ; Ubiquinone/pharmacology* ; Parkinson Disease/drug therapy* ; Dopaminergic Neurons/metabolism*

This observational cohort study investigated the potential of a novel sperm-washing medium (SWM) enriched with serotonin (5-HT), L-carnitine (L-C), and coenzyme Q10 (CoQ10) to enhance sperm motility and reduce DNA damage. It compared this innovative medium (5-HT/L-C/CoQ10 SWM) with two widely used commercial media (SWM 1 and SWM 2). Ninety-eight volunteers from an infertility clinic provided semen samples, which were divided into three aliquots for analysis in different SWMs: group 1, SWM was composed of hydroxyethyl piperazineethanesulfonic acid (HEPES), sodium bicarbonate, human serum albumin (HSA), taurine, and gentamicin sulfate (SWM 1); group 2, SWM was composed of HEPES, sodium bicarbonate, and HSA (SWM 2); and group 3, SWM was composed of HEPES-buffered human tubal fluid supplemented with 5-HT, L-C, and CoQ10 (5-HT/L-C/CoQ10 SWM). Sperm motility was categorized as progressive, nonprogressive, or immotile. Apoptosis, reactive oxygen species (ROS) production, and DNA fragmentation were also assessed. There were no significant differences in total or progressive sperm motility among the groups. Spermatozoa in group 3 exhibited reduced apoptosis, necrosis, and ROS levels and increased viability. No significant differences were observed in the DNA fragmentation index among groups. The 5-HT/L-C/CoQ10 SWM reduced sperm oxidative stress and apoptosis compared with those of the two commercially available SWMs, suggesting that 5-HT/L-C/CoQ10 SWM could be useful for enhancing in vitro fertilization success rates.
Humans ; Male ; Serotonin ; Carnitine/pharmacology* ; Ubiquinone/pharmacology* ; Sperm Motility/drug effects* ; Adult ; Spermatozoa/drug effects* ; Cohort Studies ; Reactive Oxygen Species/metabolism* ; Culture Media ; DNA Fragmentation/drug effects* ; Apoptosis/drug effects* ; DNA Damage/drug effects*

OBJECTIVES: To explore the effect of acupuncture and moxibustion on intestinal flora in the rats with diarrhea-predominant irritable bowel syndrome (IBS-D) based on 16S rDNA technique. METHODS: Ten rats were randomized from 58 SPF-grade male SD rats to be the blank group. The remained 48 rats were prepared to be IBS-D models by the modified method of acetic acid enema combined with binding tail-clip stress. Forty successfully-modeled rats were randomly divided into a model group, an acupuncture group, a moxibustion group and a western medication group, with 10 rats in each one. In the acupuncture group, the needle was inserted at bilateral "Zusanli" (ST 36) and remained for 15 min in each rat. In the moxibustion group, the suspending moxibustion was delivered at bilateral "Zusanli" (ST 36) for 15 min. The rats in the western medication group were given pinaverium bromide suspension (10 mL/kg) by intragastric administration. The above interventions were performed once daily for consecutive 14 days. The body mass and the score of fecal trait were compared before and after modeling, as well as after intervention in each group. Fecal water content, diarrhea index and colon transit time (CTT) were measured after modeling and intervention in the rats of each group separately. After intervention, the colonic morphology of rats in each group was observed, and using 16S rDNA technique, the intestinal flora was detected. RESULTS: After modeling, compared with the blank group, the body mass and CTT were reduced (P<0.01); fecal trait scores, fecal water contents and diarrhea index increased (P<0.01) in the other 4 groups. After intervention, the body mass and CTT of the rats decreased (P<0.01), and fecal trait score, fecal water content and diarrhea index increased (P<0.01) in the model group compared with those in the blank group. In the acupuncture group, the moxibustion group and the western medication group, when compared with the model group, the body mass and CTT were elevated (P<0.01), while fecal trait scores, fecal water contents and diarrhea index declined (P<0.01). Compared with the western medication group, fecal water content decreased in the acupuncture group and the moxibustion group (P<0.05), while CTT increased in the acupuncture group (P<0.01), the body mass increased and fecal trait score was dropped in the moxibustion group (P<0.05). The colonic mucosa structure was clear and complete, and there was no obvious inflammatory cell infiltration in the blank group. The mild interstitial edema of intestinal mucosa was presented with the infiltration of few inflammatory cells in the model group. There was the infiltration of few inflammatory cells in the mucosa of the acupuncture group, the moxibustion group and the western medication group. Compared with the blank group, the indexes of Richness, Chao1, ACE and Shannon decreased in the model group (P<0.05). Indexes of Richness, Chao1 and ACE increased in the acupuncture group and the moxibustion group (P<0.05), and the Richness index in the western medication group increased (P<0.05) when compared with those in the model group. The relative abundance of Bacteroidetes, Proteobacteria and Prevotella increased (P<0.05), and that of Firmicutes and Muribaculaceae decreased (P<0.05) in the model group compared with those in the blank group. When compared with the model group, the relative abundance of Bacteroidetes, Proteobacteria and Prevotella was reduced (P<0.05), while that of Firmicutes and Muribaculaceae increased (P<0.05) in the acupuncture group, the moxibustion group and the western medication group; and that of Actinobacteria and Bifidobacterium increased in the acupuncture group and the moxibustion group (P<0.05). Compared with the blank group, the relative abundance of lipopolysaccharide (LPS) biosynthesis was elevated (P<0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis decreased (P<0.05) in the model group. The relative abundance of LPS biosynthesis was dropped (P<0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis increased (P<0.05) in the acupuncture group, the moxibustion group and the western medication group compared with those of the model group. CONCLUSIONS Either acupuncture or moxibustion can relieve the symptoms of IBS-D and protect intestinal mucosa, which may be associated with regulating the structure of intestinal flora and promoting nutrient metabolism and biosynthesis.
Rats ; Male ; Animals ; Irritable Bowel Syndrome/therapy* ; Moxibustion/methods* ; Rats, Sprague-Dawley ; Gastrointestinal Microbiome ; Lipopolysaccharides ; Thioctic Acid ; Ubiquinone ; Zeatin ; Acupuncture Therapy ; Diarrhea/therapy* ; Terpenes ; Water ; Folic Acid ; Acupuncture Points

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
Animals ; Antiviral Agents ; pharmacology ; therapeutic use ; Betacoronavirus ; drug effects ; physiology ; Binding Sites ; drug effects ; Cell Line ; Coronavirus Infections ; drug therapy ; virology ; Crotonates ; pharmacology ; Cytokine Release Syndrome ; drug therapy ; Drug Evaluation, Preclinical ; Gene Knockout Techniques ; Humans ; Influenza A virus ; drug effects ; Leflunomide ; pharmacology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; Oseltamivir ; therapeutic use ; Oxidoreductases ; antagonists & inhibitors ; metabolism ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; Protein Binding ; drug effects ; Pyrimidines ; biosynthesis ; RNA Viruses ; drug effects ; physiology ; Structure-Activity Relationship ; Toluidines ; pharmacology ; Ubiquinone ; metabolism ; Virus Replication ; drug effects

OBJECTIVES: To examine the changes of coenzyme Q10 (CoQ10) and β-galactosyl transferase specific chaperone 1 (C1GALT1C1) in brain of rats with ischemic injury at different time points and to explore the protective mechanism of ultrashort wave (USW) on ischemic brain injury. METHODS: Fifty SD rats were randomly divided into 5 groups (=10 per group): a sham group (control group) and 4 experimental group (ischemia for 2 h). The 4 experimental groups were set as a model 1 d group, a USW 1 d group, a model 3 d group and a USW 3 d group, respectively. Five rats were randomly selected for 2,3,5-triphenyltetrazoliumchloride (TTC) staining in each experimental group, and the remaining 5 rats were subjected to Western blotting and real-time PCR. The percentage of cerebral infarction volume and the relative expression level of CoQ10 and C1GALT1C1 in the brain were examined and compared. RESULTS: The infarct volume percentage after TTC staining was zero in the sham group. With the progress of disease and USW therapy, the infarct volume percentage was decreased in the experimental groups (all <0.05); Western blotting and real-time PCR showed that the relative expression level of CoQ10 in the sham group was the highest, while in the experimental groups, the content of CoQ10 showed a upward trend with the extension of disease and USW therapy, with significant difference (all <0.05). The relative expression level of C1GALT1C1 in the sham group was the lowest, but in the experimental groups, they showed a downward trend with the extension of disease and USW therapy, with significant difference (all <0.05). CONCLUSIONS Non-caloric USW therapy may upregulate the expression of CoQ10 to suppress the expression of C1GALT1C1 in rats, leading to alleviating cerebral ischemic reperfusion injury.
Animals ; Brain ; Brain Ischemia ; Molecular Chaperones ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; Ubiquinone ; analogs & derivatives

Porphyromonas species are closely associated with companion animal periodontitis which is one of the most common diseases in dogs and cats and leads to serious systemic diseases if left untreated. In this study, we evaluated the antimicrobial effects and mode of action of sodium tripolyphosphate (polyP3, Na5P3O10), a food additive with proven safety, using three pathogenic Porphyromonas species. The minimum inhibitory concentrations (MICs) of polyP3 against Porphyromonas gulae, Porphyromonas cansulci, and Porphyromonas cangingivalis were between 500 and 750 mg/L. PolyP3 significantly decreased viable planktonic cells as well as bacterial biofilm formation, even at sub-MIC concentrations. PolyP3 caused bacterial membrane disruption and this effect was most prominent in P. cangingivalis, which was demonstrated by measuring the amount of nucleotide leakage from the cells. To further investigate the mode of action of polyP3, high-throughput whole-transcriptome sequencing was performed using P. gulae. Approximately 30% of the total genes of P. gulae were differentially expressed by polyP3 (> 4-fold, adjusted p value < 0.01). PolyP3 influenced the expression of the P. gulae genes related to the biosynthesis of thiamine, ubiquinone, and peptidoglycan. Collectively, polyP3 has excellent antibacterial effects against pathogenic Porphyromonas species and can be a promising agent to control oral pathogenic bacteria in companion animals.
Animals ; Bacteria ; Biofilms ; Cats ; Dogs ; Food Additives ; Friends ; Humans ; Membranes ; Microbial Sensitivity Tests ; Peptidoglycan ; Periodontitis ; Pets ; Plankton ; Porphyromonas ; Sodium ; Thiamine ; Ubiquinone

Background: Focal segmental glomerulosclerosis (FSGS) is a kidney disease that is commonly associated with proteinuria and the progressive loss of renal function, which is characterized by podocyte injury and the depletion and collapse of glomerular capillary segments. The pathogenesis of FSGS has not been completely elucidated; however, recent advances in molecular genetics have provided increasing evidence that podocyte structural and functional disruption is central to FSGS pathogenesis. Here, we identified a patient with FSGS and aimed to characterize the pathogenic gene and verify its mechanism. Methods: Using next-generation sequencing and Sanger sequencing, we screened the causative gene that was linked to FSGS in this study. The patient's total blood RNA was extracted to validate the messenger RNA (mRNA) expression of coenzyme Q monooxygenase 6 (COQ6) and validated it by immunohistochemistry. COQ6 knockdown in podocytes was performed in vitro with small interfering RNA, and then, F-actin was determined using immunofluorescence staining. Cell apoptosis was evaluated by flow cytometry, the expression of active caspase-3 was determined by Western blot, and mitochondrial function was detected by MitoSOX. Results: Using whole-exome sequencing and Sanger sequencing, we screened a new causative gene, COQ6, NM_182480: exon1: c.G41A: p.W14X. The mRNA expression of COQ6 in the proband showed decreased. Moreover, the expression of COQ6, which was validated by immunohistochemistry, also had the same change in the proband. Finally, we focused on the COQ6 gene to clarify the mechanism of podocyte injury. Flow cytometry showed significantly increased in apoptotic podocytes, and Western blotting showed increases in active caspase-3 in si-COQ6 podocytes. Meanwhile, reactive oxygen species (ROS) levels were increased and F-actin immunofluorescence was irregularly distributed in the si-COQ6 group. Conclusions This study reported a possible mechanism for FSGS and suggested that a new mutation in COQ6, which could cause respiratory chain defect, increase the generation of ROS, destroy the podocyte cytoskeleton, and induce apoptosis. It provides basic theoretical basis for the screening of FSGS in the future.
Adolescent ; Animals ; Apoptosis ; genetics ; physiology ; Cell Line ; Female ; Flow Cytometry ; Glomerulosclerosis, Focal Segmental ; genetics ; Humans ; Immunohistochemistry ; Mice ; Mutation ; genetics ; Podocytes ; metabolism ; pathology ; RNA, Messenger ; genetics ; RNA, Small Interfering ; genetics ; metabolism ; Ubiquinone ; analogs & derivatives ; genetics ; metabolism

Animals ; Apoptosis ; drug effects ; genetics ; COS Cells ; Cercopithecus aethiops ; Cytoskeletal Proteins ; genetics ; metabolism ; Eye Proteins ; genetics ; metabolism ; Glaucoma, Open-Angle ; genetics ; metabolism ; Glycoproteins ; genetics ; metabolism ; Humans ; Mutation ; Ubiquinone ; analogs & derivatives ; pharmacology

OBJECTIVE: The aim of this study was to investigate whether cortisol and oxidative stress levels and DNA damage differ between individuals who developed PTSD or not following a sexual trauma. METHODS: The study included 61 children aged between 5 and 17 years who sustained sexual abuse (M/F: 18/43). The patients were divided into two groups: patients with PTSD and patients without PTSD based, based on the results of a structured psychiatric interview (K-SADS-PL and CAPS-CA). Cortisol, glutathione peroxidase (GPx), superoxide dismutase (SOD), coenzyme Q, 8-Hydroxy-2-Deoxyguanosine (8-OHdG) were all evaluated by the ELISA method. RESULTS: Our evaluation revealed a diagnosis of PTSD in 51% (n=31) of victims. There was no significant difference between the groups with or without PTSD in terms of cortisol, GPx, SOD, coenzyme Q, and 8-OHdG levels. There was no correlation between CAPS scores and GPx, SOD, coenzyme Q, and 8-OHdG levels between patients with or without PTSD. In patients with PTSD, both cortisol and 8-OHdG levels decreased with increasing time after trauma, and there was no significant correlation with cortisol and 8-OHdG levels in patients without PTSD. CONCLUSION: Although the present study did not find any difference between the groups in terms of 8-OHdG concentrations, the decreases in both cortisol and 8-OHdG levels with increasing time after trauma is considered to indicate a relationship between cortisol and DNA damage.
Adolescent* ; Child* ; Diagnosis ; DNA Damage* ; DNA* ; Enzyme-Linked Immunosorbent Assay ; Glutathione Peroxidase ; Humans ; Hydrocortisone* ; Methods ; Oxidative Stress* ; Sex Offenses* ; Stress Disorders, Post-Traumatic* ; Superoxide Dismutase ; Ubiquinone