Physical stability of oil-in-water multi-layered coenzyme Q10 nano-emulsions.

As a lipophilic antioxidant, coenzyme Q10 (CoQ10) has limited application owing to its low water solubility and instability. In the present study, potato protein (PP) and soybean soluble polysaccharide (SSPS) were used as carriers to prepare a multilayer SSPS-PP-CoQ10 nano-emulsion using the reversed-phase emulsification method; further, the water solubility, stability, and formation mechanism of the nano-emulsion were analyzed. The results showed that the particle size of SSPS-PP-CoQ10 nano-emulsions was 253-422 nm with good polydispersity. The encapsulation efficiency (EE) could reach up to 88.87 %. When the concentration of SSPS was 0.1 wt%, the decrease in interfacial tension and increase in viscoelasticity indicated that nano-emulsion improved CoQ10 physical stability. SSPS incorporation altered the microscopic environment of the hydrophobic residues, rendering them more hydrophilic and enhancing their water solubility. According to molecular docking results, hydrogen bonds promote binding among SSPS, PP, and CoQ10, and increase emulsion stability.

Cellular oxygen consumption in patients with diabetic ketoacidosis.

BACKGROUND: Diabetic ketoacidosis (DKA) is a potentially life-threatening disorder associated with severe alterations in metabolism and acid-base status. Mitochondrial dysfunction is associated with diabetes and its complications. Thiamine and coenzyme Q10 (CoQ10) are important factors in aerobic metabolism. In this study, we measured cellular oxygen consumption rates (OCRs) and the effects of in vitro administration of thiamine and CoQ10 on OCRs in patients with DKA versus healthy controls. METHODS: Blood samples were collected from a prospective cohort of patients with DKA and from controls. Cellular OCRs were measured in peripheral blood mononuclear cells (PBMC) without treatment and after treatment with thiamine, CoQ10, or both. The mitochondrial profile was measured using an XFe96 Extracellular Flux Analyzer and XF Cell Mito Stress Test Kit (Seahorse Bioscience). A linear quantile mixed model was used to compare OCRs and estimate treatment effects. RESULTS: A total of 62 patients with DKA and 48 controls were included in the study. The median basal and maximal OCRs were lower in the DKA group than in the control group (basal: 4.7 [IQR: 3.3, 7.9] vs. 7.9 [5.0, 9.5], p = 0.036; maximal: 16.4 [9.5, 28.1] vs. 31.5 [20.6, 46.0] pmol/min/µg protein, p < 0.001). In DKA samples, basal and maximal OCRs were significantly increased when treated with thiamine, CoQ10, or both. In controls, basal and maximal OCR were significantly increased only with thiamine treatment. CONCLUSION: Mitochondrial metabolic profiles of patients with DKA demonstrated lower cellular oxygen consumption when compared to healthy controls. Oxygen consumption increased significantly in cells of patients with DKA treated with thiamine or CoQ10. These results suggest that thiamine and CoQ10 could potentially have therapeutic benefits in DKA via their metabolic effects on mitochondrial cellular respiration.

Effectiveness of Coenzyme Q10 Supplementation in Statin-Induced Myopathy: A Systematic Review.

Statins are among the most widely prescribed drugs for treating dyslipidemia and reducing the incidence of heart disease and stroke. However, they come with a wide range of side effects, from myopathy to necrotizing rhabdomyolysis, as well as diabetes, hepatotoxicity, and sleep problems. The most common side effect of statins is statin-induced myopathy, often leading to discontinuation of statin therapy and noncompliance in many patients. This study aims to assess the effectiveness of coenzyme Q10 (CoQ10) supplementation as a treatment for patients with statin-induced myopathy. This systematic review was conducted by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. Relevant studies were identified through searches of Medline, PMC, PubMed, Science Direct, and Google Scholar. Only randomized control trials and meta-analyses of oral CoQ10 supplementation versus placebo in adults with statin-associated myalgia were included. The risk of bias was assessed using the Cochrane Risk of Bias tool (The Cochrane Collaboration, London, England, UK) and the measurement tool for the "assessment of multiple systematic reviews" (AMSTAR tool). Out of 5,000 records identified, only five were selected for this review: one meta-analysis and four randomized controlled trials. All of these studies were conducted between 2010 and 2023, involving a total of 800 patients. All randomized controlled trials showed improvement in statin-associated myopathy with CoQ10 supplementation, along with or without a reduced dosage of statins, without any notable side effects of CoQ10. Therefore, it can be deduced that CoQ10 supplementation significantly ameliorates statin-induced musculoskeletal symptoms.

Effect of mitochondrial coenzyme-Q10 precursor solanesol in gentamicin-induced experimental nephrotoxicity: Evidence from restoration of ETC-complexes and histopathological alterations.

Nephrotoxicity occurs when the body is exposed to certain drugs or toxins. When kidney damage occurs, the kidney fails to eliminate excess urine and waste. Solanesol (C45H74O) is a tri-sesquiterpenoid alcohol first isolated from tobacco, and it is widely distributed in plants of the Solanaceae family. Solanesol (SNL) is an intermediate in the synthesis of coenzyme Q10 (CoQ10), an antioxidant which protects nerve cells. This study investigated the protective effect of SNL at doses of 30 and 60 mg/kg in gentamicin-induced nephrotoxicity in Wistar albino rats. Animals were distributed into six groups and administered 100 mg/kg gentamicin-intraperitoneal injection for 14 days. Biochemical assessments were performed on kidney homogenate, blood, and serum. Treatment with SNL was shown as lower serum levels of creatinine, blood urea nitrogen (BUN), thiobarbituric acid reactive substances (TBARS), and Tumor necrosis factor alpha)TNF-α ((p < .001). It also restored reduced glutathione (GSH) and mitochondrial complex enzymatic activity as protective measures against gentamicin-induced nephrotoxicity. SNL were shown to reduce inflammation and oxidative stress markers (p < .001). Histological findings furtherly augmented the protective effects of SNL. Long-term SNL therapy also restored mitochondrial electron transport chain complex enzymes, such as complex-I (p < .001). In conclusion, these findings suggest that SNL can represent a protective therapeutic option for drug-induced nephrotoxicity, a long-term adverse effect of aminoglycoside antibiotics such as gentamicin.

Two novel heterozygous HPDL variants in a Chinese family with a neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities.

Recent studies have shown that homozygous and compound heterozygous variants in the 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) gene contribute to a novel early onset neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), a severe neurodevelopmental disorder characterized by impaired psychomotor development in infancy. Using whole-exome sequencing and Sanger sequencing, we identified and verified a novel compound heterozygous variant in HPDL, c.502 T > C (p.Cys278Arg)/c.833G > A (p.Gly278Asp), which may lead to lethal NEDSWMA, with individual differences in severity. We systematically summarized the clinical characteristics of the patients and their family members and analyzed the genetic characteristics such as homozygosity, conservatism, and pathogenicity of the variants by various prediction methods. Further in vitro functional experiments showed that the identified variants inhibited the proliferative capacity but not apoptosis of SH-SY5Y cells by altering HPDL expression at the mRNA and protein levels and negatively affecting endogenous CoQ10 secretion. Our study further contributes to the assessment of genotype-phenotype correlations, and firstly provides new insights for elucidating specific pathogenesis mechanisms and identifying precision-targeted therapies.

The Spectrum of clinical manifestations in newborns with the COQ4 mutation: case series and literature review.

Background: Coenzyme Q10 (CoQ10) plays an important role in the electron transport chain within the human mitochondrial respiratory chain. The manifestations of this deficiency exhibit a diverse range. This study investigates the clinical manifestations of primary coenzyme Q10 deficiency in neonates with the COQ4 mutation to improve the diagnosis of the disease and the prognosis through targeted treatment. Methods: We report 4 patients with primary coenzyme Q10 deficiency by COQ4 variants in neonates. A comprehensive literature search and review for original articles and case reports with COQ4 mutation published from January 1989 to November 2023 was performed through Pubmed. We review clinical manifestations, diagnostic approaches, and treatment monitoring in these and 20 previously reported patients. Results: Within the cohort of four cases examined, three females and one male were identified from two distinct families. Specifically, case 1 and 2 consisted of monoamniotic twins. Cases 3 and 4 were siblings. A comprehensive review of 20 cases involving neonatal-onset COQ4 mutation was conducted. Half of the cases are Chinese. There was no statistically significant difference in the mortality between Chinese (9/12, 75%) and other regions (11/12, 91.7%) (P = 0.27). The survival time for the 24 cases was 60.0 ± 98.0 days (95% confidence interval CI: 0-252.0 days). The incidence of prenatal abnormalities in preterm infants was significantly higher than that in full-term infants (66.7% vs. 16.7%, P = 0.02). Hyperlactatemia was one of the most common manifestations, accounting for 75% of cases (18/24). Twenty of the 24 cases were diagnosed by whole exome sequencing. Only 9 patients received exogenous coenzyme Q10 treatment, and all the 4 surviving patients received coenzyme Q10 supplementation. Conclusion: The prognosis of COQ4 mutation in the neonatal period indicates a low survival rate and an poor prognosis. This may be due to the incomplete understanding of the mechanism of how COQ4 gene defects lead to coenzyme Q10 deficiency and why CoQ10 supplementation does not respond well to treatment. To improve the diagnostic rate, in addition to genetic testing, mitochondrial functional verification should be prioritized in southern China, where the incidence is relatively high. It will facilitate more in-depth mechanistic studies.

Bi-allelic variants in COQ8B, a gene involved in the biosynthesis of coenzyme Q10, lead to non-syndromic retinitis pigmentosa.

Retinitis pigmentosa (RP) is a Mendelian disease characterized by gradual loss of vision, due to the progressive degeneration of retinal cells. Genetically, it is highly heterogeneous, with pathogenic variants identified in more than 100 genes so far. Following a large-scale sequencing screening, we identified five individuals (four families) with recessive and non-syndromic RP, carrying as well bi-allelic DNA changes in COQ8B, a gene involved in the biosynthesis of coenzyme Q10. Specifically, we detected compound heterozygous assortments of five disease-causing variants (c.187C>T [p.Arg63Trp], c.566G>A [p.Trp189Ter], c.1156G>A [p.Asp386Asn], c.1324G>A [p.Val442Met], and c.1560G>A [p.Trp520Ter]), all segregating with disease according to a recessive pattern of inheritance. Cell-based analysis of recombinant proteins deriving from these genotypes, performed by target engagement assays, showed in all cases a significant decrease in ligand-protein interaction compared to the wild type. Our results indicate that variants in COQ8B lead to recessive non-syndromic RP, possibly by impairing the biosynthesis of coenzyme Q10, a key component of oxidative phosphorylation in the mitochondria.

Comparative Assessment of Beeswax Alcohol and Coenzyme Q10 (CoQ10) to Prevent Liver Aging, Organ Damage, and Oxidative Stress in Hyperlipidemic Zebrafish Exposed to D-Galactose: A 12-Week Dietary Intervention.

The current study was designed to compare in vivo efficacy between beeswax alcohol (BWA) and coenzyme Q10 (CoQ10) to treat fatty liver changes, oxidative stress, and damages in major organs of zebrafish by 12 weeks with high-cholesterol (HC) and galactose (Gal) supplementation. At week 12, the HC control and HC+Gal control groups showed 96% and 92% survivability, respectively, while co-supplementation of the 0.5% BWA and 1.0% BWA groups exhibited 96% and 100% survivability. However, co-supplementation of the 0.5% CoQ10 and 1.0% CoQ10 groups revealed the lowest survivability, around 92% and 89%, respectively. The 0.5% BWA and 1.0% BWA groups showed 21% (p < 0.001) and 41% (p < 0.001), respectively, lower total cholesterol (TC) than the HC+Gal control, while the 1.0% CoQ10 group showed only 15% lower TC than the control. Interestingly, the 0.5% BWA and 1.0% BWA groups showed 22% (p < 0.001) and 38% (p < 0.001), respectively, lower triglyceride (TG) than the HC+Gal control. However, both the 0.5% CoQ10 and 1.0% CoQ10 groups showed similar TG levels as the control, suggesting that CoQ10 supplementation had no effect on lowering serum TG. The 1.0% BWA group showed the highest plasma HDL-C and HDL-C/TC (%) up to 3.2-fold and 5.5-fold, respectively, higher than those of the HC+Gal control, while the 1.0% CoQ10 group showed 2.4-fold and 2.8-fold higher plasma HDL-C and HDL-C/TC (%), respectively, than the control. The plasma aspartate transaminase (AST) and alanine transaminase (ALT) levels were lowest in the 1.0% BWA group, 51% and 72%, respectively, lower than HC+Gal control, suggesting the lowest extent of hepatic damage. In hepatic tissue, neutrophil infiltration and interleukin (IL)-6 production were the lowest in the 1.0% BWA group, around 67% and 85%, respectively, lower than the HC+Gal control. Fatty liver change, cellular apoptosis, and cell senescence in hepatic tissue were remarkably lowered in the 1.0% BWA group, while the CoQ10 group showed much less effect than the BWA group. In kidney, ovary, and testis tissue, the 1.0% BWA group showed the lowest production of reactive oxygen species, the extent of cellular senescence, and cellular apoptosis with the healthiest cell morphology. In conclusion, supplementation of BWA remarkably protected the liver, kidney, ovary, and testis from oxidative damage by cholesterol and galactose consumption, with the least serum AST and ALT levels, inflammatory parameters, and senescence markers.

Familial thrombotic microangiopathy in a child with coenzyme Q10 deficiency-associated glomerulopathy.

We report a child with biallelic COQ6 variants presenting with familial thrombotic microangiopathy (TMA). A Chinese boy presented with steroid-resistant nephrotic syndrome at 8 months old and went into kidney failure requiring peritoneal dialysis at 15 months old. He presented with hypertensive encephalopathy with the triad of microangiopathic haemolytic anaemia, thrombocytopenia, and acute on chronic kidney injury at 25 months old following a viral illness. Kidney biopsy showed features of chronic TMA. He was managed with supportive therapy and plasma exchanges and maintained on eculizumab. However, he had another TMA relapse despite complement inhibition a year later. Eculizumab was withdrawn, and supportive therapies, including ubiquinol (50 mg/kg/day) and vitamins, were optimized. He remained relapse-free since then for 4 years. Of note, his elder sister succumbed to multiple organ failure with histological evidence of chronic TMA at the age of 4. Retrospective genetic analysis revealed the same compound heterozygous variants in the COQ6 gene.

Nonfunctional coq10 mutants maintain the ERMES complex and reveal true phenotypes associated with the loss of the coenzyme Q chaperone protein Coq10.

Coenzyme Q (CoQ) is a redox-active lipid molecule that acts as an electron carrier in the mitochondrial electron transport chain. In Saccharomyces cerevisiae, CoQ is synthesized in the mitochondrial matrix by a multisubunit protein-lipid complex termed the CoQ synthome, the spatial positioning of which is coordinated by the endoplasmic reticulum-mitochondria encounter structure (ERMES). The MDM12 gene encoding the cytosolic subunit of ERMES is coexpressed with COQ10, which encodes the putative CoQ chaperone Coq10, via a shared bidirectional promoter. Deletion of COQ10 results in respiratory deficiency, impaired CoQ biosynthesis, and reduced spatial coordination between ERMES and the CoQ synthome. While Coq10 protein content is maintained upon deletion of MDM12, we show that deletion of COQ10 by replacement with a HIS3 marker results in diminished Mdm12 protein content. Since deletion of individual ERMES subunits prevents ERMES formation, we asked whether some or all of the phenotypes associated with COQ10 deletion result from ERMES dysfunction. To identify the phenotypes resulting solely due to the loss of Coq10, we constructed strains expressing a functionally impaired (coq10-L96S) or truncated (coq10-R147∗) Coq10 isoform using CRISPR-Cas9. We show that both coq10 mutants preserve Mdm12 protein content and exhibit impaired respiratory capacity like the coq10Δ mutant, indicating that Coq10's function is vital for respiration regardless of ERMES integrity. Moreover, the maintenance of CoQ synthome stability and efficient CoQ biosynthesis observed for the coq10-R147∗ mutant suggests these deleterious phenotypes in the coq10Δ mutant result from ERMES disruption. Overall, this study clarifies the role of Coq10 in modulating CoQ biosynthesis.

Oxygen-Binding Sites of Enriched Gold Nanoclusters for Capturing Mitochondrial Reverse Electrons.

Reverse electron transfer (RET), an abnormal backward flow of electrons from complexes III/IV to II/I of mitochondria, causes the overproduction of a reduced-type CoQ to boost downstream production of mitochondrial superoxide anions that leads to ischemia-reperfusion injury (IRI) to organs. Herein, we studied low-coordinated gold nanoclusters (AuNCs) with abundant oxygen-binding sites to form an electron-demanding trapper that allowed rapid capture of electrons to compensate for the CoQ/CoQH2 imbalance during RET. The AuNCs were composed of only eight gold atoms that formed a Cs-symmetrical configuration with all gold atoms exposed on the edge site. The geometry and atomic configuration enhance oxygen intercalation to attain a d-band electron deficiency in frontier orbitals, forming an unusually high oxidation state for rapid mitochondrial reverse electron capture under a transient imbalance of CoQ/CoQH2 redox cycles. Using hepatic IRI cells/animals, we corroborated that the CoQ-like AuNCs prevent inflammation and liver damage from IRI via recovery of the mitochondrial function.

Associations between Long-Term Dietary Coenzyme Q10 Intake and New-Onset Hypertension in Adults: Insights from a Nationwide Prospective Cohort Study.

Coenzyme Q10 (CoQ10) supplementation appears to be associated with a lower blood pressure. Nevertheless, it remains unclear whether food-sourced CoQ10 will affect new-onset hypertension in general adults. This study investigated the relationship between dietary CoQ10 intake and new-onset hypertension among the general population. Participants without hypertension at baseline from the China Health and Nutrition Survey (CHNS) prospective cohort study were included (n = 11,428). Dietary CoQ10 intake was collected by validated dietary recalls and the food weighing method. Linear and non-linear relationships between dietary CoQ10 intake and new-onset hypertension were analyzed using multivariable Cox proportional hazards models and restricted cubic splines. During follow-up (median: 6 years), 4006 new-onset hypertension cases were documented. Compared with non-consumers, the hazard ratio (HR) and 95% confidence interval (CI) from quintile 2 to 4 total dietary CoQ10 were 0.83 (0.76, 0.91), 0.86 (0.78, 0.94) and 1.01 (0.92, 1.11); total plant-derived CoQ10 were 0.80 (0.73, 0.88), 1.00 (0.91, 1.09) and 1.10 (1.00, 1.20); and animal-derived CoQ10 were 0.65 (0.59, 0.71), 0.58 (0.53, 0.64) and 0.68 (0.62, 0.75). The lowest risk was found at moderate intake, with a non-linear relationship (P nonlinearity < 0.05). Furthermore, the overall inverse association was stronger among individuals without alcohol consumption or eating a low-fat diet. Moderate long-term dietary CoQ10 intake might be protective against new-onset hypertension. However, it follows a non-linear relationship and excessive intake may increase the risk of new-onset hypertension in the Chinese population.

Genetic profiles of multiple system atrophy revealed by exome sequencing, long-read sequencing and spinocerebellar ataxia repeat expansion analysis.

BACKGROUND AND PURPOSE: Multiple system atrophy (MSA) is a progressive, adult-onset neurodegenerative disorder clinically characterized by combinations of autonomic failure, parkinsonism, cerebellar ataxia and pyramidal signs. Although a few genetic factors have been reported to contribute to the disease, its mutational profiles have not been systemically studied. METHODS: To address the genetic profiles of clinically diagnosed MSA patients, exome sequencing and triplet repeat detection was conducted in 205 MSA patients, including one familial case. The pathogenicity of variants was determined according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines. RESULTS: In the familial patient, a novel heterozygous COQ2 pathogenic variant (p.Ala351Thr) was identified in the MSA pedigree. In the sporadic patients, 29 pathogenic variants were revealed in 21 genes, and the PARK7 p.Ala104Thr variant was significantly associated with MSA (p = 0.0018). Moreover, burden tests demonstrated that the pathogenic variants were enriched in cerebellar ataxia-related genes in patients. Furthermore, repeat expansion analyses revealed that two patients carried the pathogenic CAG repeat expansion in the CACNA1A gene (SCA6), one patient carried the (ACAGG)exp/(ACAGG)exp expansion in RFC1 and one carried the GAA-pure expansion in FGF14 gene. CONCLUSION: In conclusion, a novel COQ2 pathogenic variant was identified in a familial MSA patient, and repeat expansions in CACNA1A, RFC1 and FGF14 gene were detected in four sporadic patients. Moreover, a PARK7 variant and the burden of pathogenic variants in cerebellar ataxia-related genes were associated with MSA.

Nrf2/FSP1/CoQ10 axis-mediated ferroptosis is involved in sodium aescinate-induced nephrotoxicity.

Sodium aescinate (SA), an active compound found in horse chestnut seeds, is widely used in clinical practice. Recently, the incidence of SA-induced adverse events, particularly renal impairment, has increased. Our previous work demonstrated that SA causes severe nephrotoxicity via nephrocyte ferroptosis; however, the underlying mechanism remains to be fully elucidated. In the current study, we investigated additional molecular pathways involved in SA-induced nephrotoxicity. Our results showed that SA inhibited cell viability, disrupted cellular membrane integrity, and enhanced reactive oxygen species (ROS), ferrous iron (Fe2+), and malondialdehyde (MDA) levels, as well as lipid peroxidation in rat proximal renal tubular epithelial cell line (NRK-52E) cells. SA also depleted coenzyme Q10 (CoQ10, ubiquinone) and nicotinamide adenine dinucleotide (NADH) and reduced ferroptosis suppressor protein 1 (FSP1) and polyprenyltransferase (coenzyme Q2, COQ2) activity, triggering lipid peroxidation and ROS accumulation in mouse kidneys and NRK-52E cells. The overexpression of COQ2, FSP1, or CoQ10 (ubiquinone) supplementation effectively attenuated SA-induced ferroptosis, whereas iFSP1 or 4-formylbenzoic acid (4-CBA) pretreatment exacerbated SA-induced nephrotoxicity. Additionally, SA decreased nuclear factor-erythroid-2-related factor 2 (Nrf2) levels and inhibited Nrf2 binding to the -1170/-1180 bp ARE site in FSP1 promoter, resulting in FSP1 suppression. Overexpression of Nrf2 or its agonist dimethyl fumarate (DMF) promoted FSP1 expression, thereby improving cellular antioxidant capacity and alleviating SA-induced ferroptosis. These results suggest that SA-triggers renal injury through oxidative stress and ferroptosis, driven by the suppression of the Nrf2/FSP1/CoQ10 axis.

Coenzyme Q10 and Vitamin E Regulate the Bioactivity of Human Corneal Fibroblast Cells.

Purpose: Corneal fibroblasts are involved in the wound healing of the cornea with proliferation, migration, and differentiation processes. Coenzyme Q10 (CoQ10) and vitamin E can enhance corneal wound healing when applied after a corneal lesion as an eye drop. Thus, this study was performed to determine the potential efficiency of a CoQ10 ophthalmical solution containing a CoQ10 and vitamin E D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-derived formulation in human corneal fibroblasts (HCFs) in vitro. Methods: Primary HCFs were obtained from cadaveric corneal tissue, and cell viability was determined using MTT assay at 24 and 72 h. Cell migration was evaluated using an in vitro wound healing assay, and mRNA expressions of collagen type I (COL-I), collagen type III (COL-III), lumican, hyaluronan, matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, tissue inhibitors of MMP (TIMP)-1, TIMP-2, interleukin (IL)-1ß, IL-6, IL-8, and IL-10 were assessed using reverse transcription polymerase chain reaction at 24 and 72 h. Results: At various concentrations of CoQ10 ophthalmical solution (CoQ10-os), cell viability and wound healing rates of HCFs increased compared with the control group. The expressions of COL-I, COL-III, lumican, and hyaluronan were increased by CoQ10-os, whereas those of MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2, and TIMP-3 were not affected by CoQ10-os at 24 and 72 h. In treating HCFs with a CoQ10-os medium, IL-1ß, IL-6, and IL-8 decreased, whereas IL-10 was significantly increased in a time- and dose-dependent manner. Conclusions: The findings indicate that CoQ10 and vitamin E-TPGS are potent regulators of the bioactivity of HCFs, thus supporting their potential application as ophthalmical solutions in therapies aimed at the fast regeneration of damaged cornea tissues.

Alterations in coenzyme Q10 status in a cybrid line harboring the 3243A>G mutation of mitochondrial DNA is associated with abnormal mitochondrial bioenergetics and dysregulated mitochondrial biogenesis.

Mitochondrial DNA (mtDNA) mutations, including the m.3243A>G mutation that causes mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), are associated with secondary coenzyme Q10 (CoQ10) deficiency. We previously demonstrated that PPARGC1A knockdown repressed the expression of PDSS2 and several COQ genes. In the present study, we compared the mitochondrial function, CoQ10 status, and levels of PDSS and COQ proteins and genes between mutant cybrids harboring the m.3243A>G mutation and wild-type cybrids. Decreased mitochondrial energy production, defective respiratory function, and reduced CoQ10 levels were observed in the mutant cybrids. The ubiquinol-10:ubiquinone-10 ratio was lower in the mutant cybrids, indicating blockage of the electron transfer upstream of CoQ, as evident from the reduced ratio upon rotenone treatment and increased ratio upon antimycin A treatment in 143B cells. The mutant cybrids exhibited downregulation of PDSS2 and several COQ genes and upregulation of COQ8A. In these cybrids, the levels of PDSS2, COQ3-a isoform, COQ4, and COQ9 were reduced, whereas those of COQ3-b and COQ8A were elevated. The mutant cybrids had repressed PPARGC1A expression, elevated ATP5A levels, and reduced levels of mtDNA-encoded proteins, nuclear DNA-encoded subunits of respiratory enzyme complexes, MNRR1, cytochrome c, and DHODH, but no change in TFAM, TOM20, and VDAC1 levels. Alterations in the CoQ10 level in MELAS may be associated with mitochondrial energy deficiency and abnormal gene regulation. The finding of a reduction in the ubiquinol-10:ubiquinone-10 ratio in the MELAS mutant cybrids differs from our previous discovery that cybrids harboring the m.8344A>G mutation exhibit a high ubiquinol-10:ubiquinone-10 ratio.

Antioxidants and Fertility in Women with Ovarian Aging: A Systematic Review and Meta-Analysis.

Ovarian aging is a major factor for female subfertility. Multiple antioxidants have been applied in different clinical scenarios, but their effects on fertility in women with ovarian aging are still unclear. To address this, a meta-analysis was performed to evaluate the effectiveness and safety of antioxidants on fertility in women with ovarian aging. A total of 20 randomized clinical trials with 2617 participants were included. The results showed that use of antioxidants not only significantly increased the number of retrieved oocytes and high-quality embryo rates but also reduced the dose of gonadotropin, contributing to higher clinical pregnancy rates. According to the subgroup analysis of different dose settings, better effects were more pronounced with lower doses; in terms of antioxidant types, coenzyme Q10 (CoQ10) tended to be more effective than melatonin, myo-inositol, and vitamins. When compared with placebo or no treatment, CoQ10 showed more advantages, whereas small improvements were observed with other drugs. In addition, based on subgroup analysis of CoQ10, the optimal treatment regimen of CoQ10 for improving pregnancy rate was 30 mg/d for 3 mo before the controlled ovarian stimulation cycle, and women with diminished ovarian reserve clearly benefited from CoQ10 treatment, especially those aged <35 y. Our study suggests that antioxidant consumption is an effective and safe complementary therapy for women with ovarian aging. Appropriate antioxidant treatment should be offered at a low dose according to the patient's age and ovarian reserve. This study was registered at PROSPERO as CRD42022359529.

Role of Dietary Antioxidant Supplements in Male Infertility: A Review.

Infertility, which affects around 70 million couples globally, is the inability to conceive after at least a year of continuous, unprotected sexual activity. Male-related elements are involving half of all infertility cases globally. Male infertility has various characteristics, including oligospermia, asthenozoospermia, and teratozoospermia. The purpose of this study was to assess the impact of antioxidant-rich food supplements on the properties of semen, like concentration of sperm, morphology, motility, fertility rate, and damage of DNA. Terms such as coenzyme Q10, antioxidants, folic acid, vitamin C, vitamin E, male infertility, selenium and others, were used to search for relevant research papers in the PubMed database. The findings of this study demonstrated beneficial improvements in semen parameters among infertile men who consumed dietary supplements, particularly combining antioxidants like coenzyme Q10, vitamin C, and vitamin E.

Evaluating the efficacy of ubiquinol in heart failure patients: a systematic review and meta-analysis.

Aim: We aim to analyze past literature to evaluate the efficacy of coenzyme Q10 (CoQ-10) in the population with heart failure (HF). Methods: A systematic literature search was conducted through MEDLINE (via PubMed) and Cochrane Library. The outcomes analyzed were a reduction in HF-related mortality, an improvement in exercise capacity, and the left ventricular ejection fraction (LVEF). Results: Among 16 studies, CoQ-10 significantly reduced HF-related mortality by 40% and improved exercise capacity in patients with HF, but demonstrated no significant difference in LVEF however, the potential of its efficacy on LVEF could not be ruled out. Conclusion: CoQ-10 significantly enhances exercise capacity and reduces HF-related mortality; however, its impact on patients with reduced LVEF requires further investigation.

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Gastroprotective and microbiome-modulating effects of ubiquinol in rats with radiation-induced enteropathy.

Radiation enteritis is a frequently encountered issue for patients receiving radiotherapy and has a significant impact on cancer patients' quality of life. The gut microbiota plays a pivotal role in intestinal function, yet the impact of irradiation on gut microorganisms is not fully understood. This study explores the gastroprotective effect and gut microbiome-modulating potential of ubiquinol (Ubq), the reduced form of the powerful antioxidant CoQ-10. For this purpose, male albino rats were randomly assigned to four groups: Control, IRR (acute 7 Gy γ-radiation), Ubq_Post (Ubq for 7 days post-irradiation), and Ubq_Pre/Post (Ubq for 7 days pre and 7 days post-irradiation). The fecal microbiomes of all groups were profiled by 16S rRNA amplicon sequencing followed by bioinformatics and statistical analysis. Histopathological examination of intestinal tissue indicated severe damage in the irradiated group, which was mitigated by ubiquinol with enhanced regeneration, goblet cells, and intestinal alkaline phosphatase expression. Compared to the irradiated group, the Ubq-treated groups had a significant recovery of intestinal interleukin-1ß, caspase-3, nitric oxide metabolites, and thio-barbituric reactive substances to near-healthy levels. Ubq_Pre/Post group displayed elevated peroxisome proliferator-activated receptor (PPAR-γ) level, suggesting heightened benefits. Serum insulin reduction in irradiated rats improved post-Ubq treatment, with a possible anti-inflammatory effect on the pancreatic tissue. Fecal microbiota profiling revealed a dysbiosis state with a reduction of bacterial diversity post-irradiation, which was re-modulated in the Ubq treated groups to profiles that are indistinguishable from the control group. These findings underscore Ubq's gastroprotective effects against radiation-induced enteritis and its potential in restoring the gut microbiota's diversity and balance.