Search Results (205)

Background/Objectives: Heart failure remains a complex syndrome with high morbidity and mortality, highlighting the urgent need for alternative treatments that address underlying bioenergetic impairments. CoQ10, which plays a crucial role in mitochondrial ATP production, has shown promising results in small studies, although larger trials are needed to confirm its efficacy. Results: This randomized controlled trial investigated the effects of coenzyme Q10 (CoQ10) supplementation on cardiac function and quality of life in heart failure patients. A total of 120 patients were randomly assigned to receive either CoQ10 (2 × 60 mg daily) or a placebo for six months. Baseline characteristics were similar between groups. The primary outcomes were changes in global longitudinal strain (GLS) and left ventricular ejection fractions (LVEFs), while secondary outcomes included improvements in functional capacity and quality of life. At the 6-month endpoint, the CoQ10 group showed significant improvements in GLS (−11.7% to −14.9%, p < 0.001), NT-proBNP levels (815.6 vs. 1378.5 pg/mL, p = 0.012), blood pressure, and 6 min walk test distance (349.3 vs. 267.0 m, p = 0.008) compared to the placebo group. LVEFs improved slightly in the CoQ10 group (38.9% to 40.6%, p = 0.170) but remained unchanged in the placebo group. Conclusions: These findings suggest that CoQ10 supplementation may improve cardiac function, reduce cardiac stress, and enhance functional capacity and quality of life in heart failure patients. Further research is needed to optimize dosage and identify the subgroups that may benefit most from CoQ10 therapy. Full article

Global kelp farming is garnering growing attention for its contributions to fishery yields, environmental remediation, and carbon neutrality efforts. Kelp farming systems face escalating pressures from compounded climatic and environmental stressors. A severe outbreak disaster caused extensive kelp mortality and significant economic losses in Rongcheng, China, one of the world’s largest kelp farming areas. This study investigated the growth and physiological responses of Saccharina japonica to combined stressors involving three levels of N:P ratios (10:1 as a control; 100:1 and 500:1 to represent phosphorus deficiency stress) and two temperature/light regimes (12 °C, 90 μmol photons m⁻² s⁻¹ as a control, and 17 °C, 340 μmol photons m⁻² s⁻¹ to represent thermal and high-light stress). The results demonstrated that phosphorus deficiency significantly inhibited the relative growth rate of kelp (24% decrease), and the strongest growth inhibition in kelp was observed at the N:P ratio of 500:1 combined with thermal and high-light stress. The algal tissue was whitened due to its progressive disintegration under escalating stress, coupled with damage to its chloroplasts and nucleus ultrastructures. Phosphorus-deficiency-induced declines in photochemistry (27–56% decrease) and chlorophyll content (63% decrease) were paradoxically and transiently reversed by thermal and high-light stress, but this “false recovery” accelerated subsequent metabolic collapse (a 60–75% decrease in the growth rate and a loss of thallus integrity). Alkaline phosphatase was preferentially activated to cope with phosphorus deficiency combined with photothermal stress, while acid phosphatase was subsequently induced to provide auxiliary support. S. japonica suppressed its metabolism but upregulated its nucleotides under phosphorus deficiency; however, the energy/amino acid/coenzyme pathways were activated and a broad spectrum of metabolites were upregulated under combined stressors, indicating that S. japonica employs a dual adaptive strategy where phosphorus scarcity triggers metabolic conservation. Thermal/light stress can override phosphorus limitations by activating specific compensatory pathways. The findings of this study provide a foundation for the sustainable development of kelp farming under climate and environmental changes. Full article

Objectives: This study aims to elucidate the metabolic differences between obese adolescents categorized into low-weight-loss (LWL) and high-weight-loss (HWL) groups. Methods: The objective of this study is to investigate the metabolic characteristics of obese adolescents, with a focus on the statistically significant individual differences observed in weight loss outcomes after the same dietary and exercise training intervention. A four-week exercise and dietary intervention was administered to the participants. Obese adolescents were categorized into LWL (with a weight loss percentage of 5–10%) and HWL (with a weight loss percentage of >10%) groups on the basis of their weight loss outcomes. Post-intervention changes in body morphology and body composition between the two groups were compared using Analysis of Covariance (ANCOVA), with gender as a covariate. Additionally, metabolic changes were analyzed in depth; differential metabolites between the groups were identified through ANCOVA adjusted for gender, followed by pathway analysis. Results: After the four-week exercise intervention, the body morphology and composition of the obese adolescents showed significant improvements compared with those before the intervention (p < 0.001). For example, weight decreased from 80.65 kg to 72.35 kg, BMI decreased from 30.57 kg/m² to 27.26 kg/m², waist circumference decreased from 103.64 cm to 94.72 cm, and body fat percentage decreased from 32.68% to 28.54%. Prior to the exercise intervention, no significant differences in body morphology and composition were observed between the HWL and LWL groups (p > 0.05). After the intervention, the HWL group demonstrated significant improvements in weight, body mass index, waist circumference, body fat percentage, fat mass, fat-free mass, body water amount, and skeletal muscle mass compared with the LWL group (p < 0.001). After controlling for the levels of pre-intervention metabolites, 27 differential metabolites were identified between the HWL and LWL groups. These metabolites were categorized into fatty acids, amino acids, organic acids, carnitines, indoles, benzoic acids, and carbohydrates. Notably, they were significantly enriched in the eight metabolic pathways involved in amino acid metabolism, fatty acid biosynthesis, and coenzyme A biosynthesis. Conclusions: A four-week exercise intervention enhanced the body morphology and physical fitness of obese adolescents, although the degree of weight loss varied among individuals. Considerable weight reduction was significantly correlated with metabolites involved in lipid, amino acid, organic acid, carbohydrate, and gut microbiota metabolism and with the enrichment of pathways involved in amino acid metabolism, fatty acid biosynthesis, and coenzyme A biosynthesis. These findings indicate that intrinsic metabolic characteristics considerably influence individual responsiveness to exercise-based weight-loss interventions. Full article

Direct interspecies electron transfer (DIET) is a syntrophic metabolism wherein free electrons are directly transferred between microorganisms without the mediation of intermediates such as molecular hydrogen or formate. Previous research has demonstrated that Methanothrix harundinacea 6Ac is capable of reducing carbon dioxide through DIET. However, the mechanisms underlying electron uptake in M. harundinacea 6Ac during DIET remain poorly understood. This study aims to elucidate the electron and proton flux in M. harundinacea 6Ac during DIET and to propose a model for electron uptake in this organism, primarily based on the analysis of gene transcript levels, genomic characteristics of M. harundinacea 6Ac, and the pathways generating fully reduced ferridoxin (Fd_red²⁻), reduced coenzyme F₄₂₀ (F₄₂₀H₂), coenzyme M (CoM-SH), and coenzyme B (CoB-SH) during DIET. The findings suggest that membrane-bound heterodisulfide reductase (HdrED), F₄₂₀H₂-dehydrogenase lacking subunit F (Fpo⁻), and cytoplasmic heterodisulfide reductase (HdrABC)-subunit B of F₄₂₀-reducing hydrogenase (FrhB) complex play critical roles in electron uptake in M. harundinacea 6Ac during DIET. Specifically, Fpo⁻ is responsible for generating Fd_red²⁻ with reduced methanophenazine (MPH₂), driven by a proton motive force, while HdrED facilitates the reduction of heterodisulfide of coenzyme M and coenzyme B (CoM-S-S-CoB) to CoM-SH and CoB-SH using MPH₂. Additionally, cytoplasmic heterodisulfide reductase HdrABC and subunit B of coenzyme F₄₂₀-hydrogenase complex (HdrABC-FrhB complex) catalyzes the reduction of oxidized coenzyme F₄₂₀ (F₄₂₀) to F₄₂₀H₂, utilizing CoM-SH, CoB-SH, and Fd_red²⁻. This study represents the first genetics-based functional characterization of electron and proton flux in M. harundinacea 6Ac during DIET, providing a model for further investigation of electron uptake in Methanosaeta species. Furthermore, it deepens our understanding of the mechanisms underlying electron uptake in methanogens during DIET. Full article

Anaerobic digestion (AD) of high-solid mono-chicken manure (CM) holds great promise for resource utilization. However, the effects of substrate overload (high-solid mixture inside the reactor) on AD performance at various temperatures are still unclear, moreover, the metabolic processes with and without inoculation are also seldom reported. In this study, three key impact factors of different temperatures (4 °C, 35 °C, 55 °C and 75 °C), total solids (TS) inside, and inoculation were conducted to comprehensively explore the process variation. EEM-FRI results revealed that high temps boost coenzyme F_420, while TS predominately driver the microbial production. High TS and temperature synthetically result in high free ammonia (FA) (>600 mg/L) associated with free volatile fatty acid (FVFA) (>450 mg/L), reducing CH₄ production but increasing VFAs accumulation (12 g/L at 55 °C). Notably, intestinal microbiota alone without inoculation even achieved 11 g/L of VFA. The cross-feeding symbiosis between fermentative bacteria (Caldicoprobacter, Bacteroidetes, Tepidimicrobium) and hydrogenotrophic Methanobacterium enhanced CH₄ production (68 mL/gVS at 35 °C). Moreover, high temperatures reduced microbial diversity but made heat-resistant hydrolytic bacteria dominant. This study precisely analyzes the effects of temperature and inoculation factors on the acidification efficiency of high-solid CM digestion, providing a crucial scientific basis for optimizing the resource utilization of CM waste. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder. Camellia seed cake, a byproduct of oil extraction, contains a variety of bioactive compounds. This study investigated the regulatory effects and underlying mechanisms of camellia seed cake extract (CSCE) using a high-fat diet (HFD)-induced MASLD mouse model. Methods: Mice were divided into four groups: normal control (N, standard diet), HFD model (M), HFD-fed mice treated with low-dose CSCE (L), and HFD-fed mice treated with high-dose CSCE (H). CSCE was administered via oral gavage for eight weeks. Body weight, blood lipid levels, liver weight, hepatic lipid accumulation, oxidative stress markers, ATP levels, and the NADH/NAD⁺ ratio were measured. Transcriptomic and lipidomic analyses were performed to identify potential regulatory pathways, and qPCR analysis was conducted to confirm the expression levels of essential genes. Results: CSCE significantly reduced HFD-induced increases in body and liver weights, improved blood lipid profiles and hepatic lipid accumulation, alleviated oxidative stress, increased ATP levels, and reduced the NADH/NAD⁺ ratio. Transcriptomic analysis demonstrated notable enrichment of genes associated with oxidative phosphorylation, mitochondrial function, and lipid metabolism after treatment. The lipidomic analysis demonstrated that the hepatic lipid profile of the H group approached that of the N group, with Coenzyme Q9 (CoQ9) and Coenzyme Q10 (CoQ10) levels significantly increased by 173.32% and 202.73%, respectively, compared to the M group. qPCR validation confirmed that CoQ synthesis-related genes (Coq2–10, Pdss1, Pdss2, and Hmgcr) were significantly upregulated in the treatment groups. Conclusions: CSCE enhances mitochondrial function by promoting CoQ synthesis, alleviates metabolic dysfunction, and could represent a potential natural intervention for MASLD. Full article

The cholesterol biosynthesis pathway is upregulated during breast cancer development and progression. Inhibition of the aberrantly upregulated cholesterol pathway by statins reduces breast tumor incidence and burden by 50% in SV40 C3(1) TAg mice, a mouse model of triple negative breast cancer. We hypothesized that fluvastatin’s preventive efficacy could be further enhanced by co-targeting the statin-induced restorative feedback pathways that tightly control the cholesterol pathway and are involved in resistance to statins. Acyl-coenzyme A: cholesterol acyltransferase (ACAT)2 is a cholesterol esterification gene that is upregulated in statin-resistant MCF10.DCIS cells, and in mammary tumors of statin-non-responsive SV40 C3(1) TAg mice. In support of this hypothesis, a combination of fluvastatin and avasimibe effectively inhibited the cell growth of statin-resistant MCF10.DCIS cells. However, this combination failed to prevent breast tumor formation in SV40 C3(1) TAg mice. Although avasimibe inhibited fluvastatin-induced ACAT2 mRNA expression in the breast tissue of the combination-treated mice, confirming that avasimibe effectively hit its target, the fluvastatin and avasimibe combination was completely ineffective in preventing breast cancer in vivo, with approximately 90% of mice developing tumors by 22 weeks, similar to the vehicle control group animals. These findings, along with avasimibe’ s known interactions with CYP450 gene family members, suggest that AVA abrogates the efficacy of fluvastatin through enhanced metabolism of fluvastatin in vivo. The findings reported in this brief communication provide a cautionary note for studies proposing the use of avasimibe in combination therapy for cancer prevention and treatment. Full article

Colorectal cancer (CRC) is recognized as the third most lethal cancer worldwide. While existing treatment options demonstrate considerable efficacy, they are often constrained by non-selectivity and substantial side effects. Recent studies indicate that lipid metabolism significantly influences carcinogenesis, highlighting it as a promising avenue for developing targeted anticancer therapies. The purpose of the study was to see if acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), and stearoyl-CoA 9-desaturase (SCD1) are good metabolic targets and whether the use of inhibitors of these enzymes together with 5-fluorouracil (5-FU) would have a synergistic effect on CRC cell viability. To confirm that the correct lipid targets were chosen, the expression levels of ACAT1, HMGCR, and SCD1 were examined in CRC patients and cell models. At first, each compound (Avasimibe, Lovastatin, MF-438, and 5-FU was tested separately, and then each inhibitor was paired with 5-FU to assess the synergistic effect on cell viability. Gene expression of selected enzymes significantly increased in tissue samples obtained from CRC patients and cancer cell lines (HT-29). Inhibition of any of the selected enzymes reduced CRC cell growth in a dose-dependent manner. More importantly, the combination of 5-FU + Avasimibe (an ACAT1 inhibitor) and 5-FU + MF-438 (an SCD1 inhibitor) produced a stronger antiproliferative effect than the inhibitors alone. 5-FU combined either with Avasimibe or MF-438 showed a synergistic effect with an HSA score of 47.00 at a dose of 0.3 + 30 µM, respectively (2.66% viability rate vs. 46%; p < 0.001), and 39.34 at a dose of 0.3 + 0.06 µM (46% vs. 10.33%; p < 0.001), respectively. The association of 5-FU with Lovastatin (HMGCR inhibitor) did not significantly impact CRC cell viability in a synergistic manner. Inhibition of lipid metabolism combined with standard chemotherapy is a promising strategy that reduces CRC cell viability and allows for the use of a lower drug dose. The combination of 5-FU and Avasimibe has the greatest therapeutic potential among studied compounds. Full article

A novel Bacillus subtilis HB-31 strain was isolated from Gotjawal Wetland in Jeju Island, Republic of Korea. A mucus substance produced by this strain was identified as high-molecular-weight poly-γ-glutamic acid (γ-PGA) using NMR, Fourier transform infrared spectroscopy, and size-exclusion chromatography/multi-angle light scattering analyses. We evaluated whether γ-PGA strengthened the skin barrier using keratinocytes and a reconstructed skin model. In keratinocytes, γ-PGA treatment dose-dependently increased the mRNA expression of skin barrier markers, including filaggrin, involucrin, loricrin, serine palmitoyl transferase, fatty acid synthase, and 3-hydroxy-3-methylglutaryl coenzyme A reductase. γ-PGA also enhanced hyaluronic acid synthesis by upregulating hyaluronic acid synthase-1, -2, and -3 mRNA levels and promoted aquaporin 3 expression, which is involved in skin hydration. In the reconstructed skin model, topical application of 1% γ-PGA elevated filaggrin, involucrin, CD44, and aquaporin 3 expression, compared to the control. These results suggest that the newly isolated HB-31 can be used as a commercial production system of high-molecular-weight γ-PGA, which can serve as an effective ingredient for strengthening the skin barrier and improving moisture retention. Further research is needed to explore the long-term effects of γ-PGA on skin health and its application in treating skin conditions. Full article

Rising global food demand necessitates improved crop yields. Biostimulants offer a potential solution to meet these demands. Among them, antioxidants have shown potential to improve yield, nutritional quality, and resilience to climate change. However, large-scale production of many antioxidants is challenging. Here, we investigate Coenzyme M (CoM), a small, achiral antioxidant from archaea, as a potential biostimulant, investigating its effects on growth and physiology. CoM significantly increased shoot mass and root length of the model plant, Arabidopsis thaliana, in a concentration-dependent manner. Sulfur-containing CoM supplementation restored growth under sulfur-limited conditions in Arabidopsis, whereas similar recovery was not observed for other macronutrient deficiencies, consistent with it being metabolized. In tobacco, CoM increased photosynthetic light capture capacity, consistent with observed growth improvements. Interestingly, this effect was independent of carbon capture rates. Furthermore, CoM promoted early-stage shoot growth in various crops species, including tobacco, basil, cannabis, and soybean. Our results suggest CoM is a promising, scalable biostimulant with potential to modify photosynthesis and enhance crop productivity. Full article

Prostate cancer (PCa) is a high-prevalence disease usually characterized by metastatic spread to the pelvic lymph nodes and bones and the development of visceral metastases only in the late stages of disease. Positron Emission Tomography (PET) plays a key role in the detection of PCa metastases. Several PET radiotracers are used in PCa patients according to the stage and pathological features of the disease, in particular ⁶⁸Ga/¹⁸F-prostate-specific membrane antigen (PSMA) ligands. Moreover, 2-deoxy-2-[18F]fluoro-D-glucose ¹⁸F-FDG PET usually shows metastases in the late stages of disease, when dedifferentiated neoplastic clones lose PSMA expression. In some cases, PCa patients may present atypical sites of metastases, with uncommon appearance at PET imaging with different radiotracers. We present the case of a patient with biochemical recurrence of PCa (ISUP Grade Group IV; PSA 4.7 ng/mL) showing atypical sites of metastases (the testis and multiple lung nodules) with absent PSMA expression and high [¹⁸F]FDG avidity. The patient showed diffuse positivity to alpha-methylacyl-coenzyme A racemase (AMACR). Moreover, a literature review was performed by collecting cases of PCa patients with atypical metastatic spread detected via PET imaging, with the aim of highlighting the relationship between atypical sites of metastases, imaging presentation, and pathology findings. Full article

This study investigated the effects of coenzyme Q10 (CoQ10) supplementation on in vitro oocyte maturation, lipid peroxidation, and embryonic development in prepubertal and aging Thai–Holstein cows. First, we used slaughterhouse-derived oocytes to confirm that CoQ10 (50 μM) significantly enhanced cleavage (53.33% vs. 37.50%) and blastocyst formation rates (46.81% vs. 27.50%). Thereafter, oocytes were collected from four prepubertal and four aging cows via ovum pick-up and matured in vitro with or without CoQ10 supplementation. The follicular development and oocyte quality were assessed. Aging cows exhibited significantly more follicles (24.00 vs. 16.67) and greater oocyte recovery (16.67 vs. 11.67) than prepubertal cows. Additionally, CoQ10 supplementation significantly reduced malondialdehyde levels in aging cows (1.28 vs. 0.61 nmol/mL), indicating reduced lipid peroxidation. Finally, CoQ10 significantly improved cleavage rates in both age groups (prepubertal: 22.50 to 32.50%; aging: 41.71 to 65.00%) and blastocyst formation rates in aging cows (prepubertal: 17.50 to 20.00%; aging: 31.44 to 53.72%). These results suggest that CoQ10 supplementation enhances oocyte maturation and embryonic development, particularly in aging cows, likely by mitigating oxidative stress and supporting mitochondrial function. Therefore, CoQ10 may be a valuable supplement in assisted reproductive technologies for improving reproductive efficiency in cattle breeding programs. Full article

This work presents the development of an amperometric biosensor for detecting aspartate aminotransferase (AST) activity in biological fluids using a platinum disk electrode as the working transducer. Optimal concentrations of substrates (aspartate, α-ketoglutarate) and the coenzyme (pyridoxal phosphate) were determined to ensure efficient biosensor operation. A semi-permeable poly-m-phenylenediamine membrane was applied to enhance selectivity against electroactive interferents. The biosensor demonstrated good stability (storage, continuous operation, and production reproducibility) and analytical performance (sensitivity 8.56 nA/min for 50 U/L AST, LOD 1 U/L, linear range 1–110 U/L). Testing with real samples showed a high correlation (R = 0.989) with spectrophotometric analysis, supporting its potential for further applications. Full article

Background: Lacticaseibacillus paracasei (L. paracasei) strains and their postbiotics show potential for managing metabolic disorders such as diabetes and obesity. Two newly isolated L. paracasei strains, M2.1 and P4, were yielded from Formica rufa anthills in Sinite Kamani National Park, Bulgaria. Their metabolic effects on mature 3T3-L1 adipocytes were investigated. Methods: Mature 3T3-L1 adipocytes were treated for 24 h with 10% (v/v) cell-free supernatants (CFSs) of M2.1 or P4. Two experimental (M2.1, P4) and two control groups (mature, untreated adipocytes and mature adipocytes, treated with 10% (v/v) MRS broth) were analyzed for intracellular lipid accumulation, glucose uptake, and the mRNA expression of lipid metabolism and beta-oxidation-related genes. Fold changes in gene expression were assessed using RT-qPCR. Results: Both M2.1 and P4 CFSs enhanced glucose uptake by over 30% compared to the control. P4 demonstrated a more favorable effect by significantly upregulating adipose triglyceride lipase–patatin-like phospholipase domain containing 2, adiponectin, and peroxisomal beta-oxidation enzymes—acyl-coenzyme A oxidase 1, palmitoyl. Intracellular lipid accumulation increased only with M2.1, while P4 supported improved lipid turnover without promoting excessive lipid storage or lipolysis. Conclusions: P4 CFS exhibits the potential to improve adipocyte metabolism by enhancing glucose uptake, promoting beta-oxidation, and increasing adiponectin expression, offering a promising strategy for managing metabolic dysfunctions. Full article

Buckwheat possesses significant nutritional content and contains different bioactive compounds, such as total flavonoids, which enhance its appeal to consumers. This study employed single-factor experiments and the response surface methodology to identify the optimal germination conditions for enhancing the total flavonoid content in buckwheat sprouts through ultraviolet-B treatment. The research showed that buckwheat sprouts germinated for 3 days at a temperature of 28.7 °C while being exposed to ultraviolet-B radiation at an intensity of 30.0 μmol·m⁻²·s⁻¹ for 7.6 h per day during the germination period resulted in the highest total flavonoid content of 1872.84 μg/g fresh weight. Under these specified conditions, ultraviolet-B treatment significantly elevated the activity and gene expression levels of enzymes related to the phenylpropanoid metabolic pathway, including phenylalanine ammonia-lyase, cinnamic acid 4-hydroxylase, 4-coumarate coenzyme A ligase, and chalcone isomerase. Ultraviolet-B treatment caused oxidative damage to buckwheat sprouts and inhibited their growth, but ultraviolet-B treatment also enhanced the activity of key enzymes in the antioxidant system, such as catalase, peroxidase, superoxide dismutase, and ascorbate peroxidase. This research provided a technical reference and theoretical support for enhancing the isoflavone content in buckwheat sprouts through ultraviolet-B treatment. Full article