Search Results (1,721)

Colorectal cancer (CRC) is the second most prevalent cancer globally and remains a significant cause of cancer-related mortality. The limited efficacy and toxicities of conventional therapies underscore the urgent need for novel treatments. Lonidamine (LND), a synthetic indazole-3-carboxylic acid derivative, possesses anticancer properties, yet its clinical use is limited by toxic side effects. Apigenin (AP), a naturally occurring flavonoid present in a variety of fruits and vegetables, has been observed to enhance the efficacy of conventional chemotherapy regimens while mitigating associated side effects. In this study, we explored the potential synergistic anticancer effects and mechanisms of combining LND with AP in colon cancer cell lines MC38 and CT26. The results showed that LND and AP in combination synergistically inhibited the growth of colon cancer cells. In vitro, the combination therapy inhibited cell migration, induced cell cycle arrest in the G2/M phase, and promoted apoptosis by downregulating Bcl-2 and upregulating Bax expression. It disrupted glycolysis by reducing HK2 and GLUT1 expression, resulting in decreased glucose consumption and lactate production. Additionally, our findings suggested that the co-administration led to nucleotide depletion and disrupted NAD⁺ metabolism. The synergistic anticancer effect of LND combined with AP was also validated in MC38 tumor-bearing mice. These findings provide preliminary evidence that the combination of LND and AP may exert beneficial effects against CRC. Full article

This study investigated the effects of high (atmospheric) and low (5% O₂) oxygen tension, as well as a combination of the two, on oocyte metabolism and quality during maturation. Cumulus cell–oocyte complexes collected from gilt ovaries were used for in vitro maturation. In addition, RNA-seq was conducted on the cumulus cells. Low oxygen tension throughout oocyte maturation did not alter the developmental rate to the blastocyst stage; however, it increased oocyte ATP and lipid content while reducing mitochondrial reactive oxygen species and mitochondrial membrane potential. Low-oxygen conditions increased glucose consumption but reduced mitochondrial DNA copy number and mitochondrial protein in cumulus cells. RNA-seq of cumulus cells revealed that low oxygen tension reduced mitochondrial activity and increased glycolysis, with the upregulation of glycolytic genes and downregulation of oxidative phosphorylation and steroidogenesis-related genes. In addition, a two-step oxygen protocol with low (5%) for the first period (0–21 h) and high (20%) for the last half period (21–44 h) increased the ATP and lipid content in oocytes and improved the embryonic developmental ability of the oocytes compared to the high-oxygen group. In conclusion, low oxygen tension during the first part of the maturation period is beneficial for oocyte quality, considering the observed metabolic changes. Full article

Background/Objectives: Aging is characterized by progressive physiological and metabolic decline. Aerobic exercise mitigates age-related impairments, and nicotinamide mononucleotide (NMN), a precursor in the NAD⁺ salvage pathway, has emerged as a nutritional intervention to promote healthy aging. This study investigated whether NMN supplementation combined with aerobic exercise provides synergistic benefits on physical performance and metabolic regulation in aged mice. Methods: Forty male C57BL/6J mice, including eight young (8 weeks) and thirty-two aged (85 weeks) mice, were randomly assigned to five groups: young sedentary (YS), aged sedentary (AS), aged with exercise (AE), aged with NMN (ASNMN; 300 mg/kg/day), and aged with combined NMN and exercise (AENMN). Interventions lasted six weeks. Assessments included grip strength, muscle endurance, aerobic capacity, oral glucose tolerance test (OGTT), and indirect calorimetry, followed by biochemical and molecular analyses of NAMPT and SirT1 expression. Results: The AENMN group demonstrated significant improvements in maximal strength and aerobic endurance compared with the AS group (p < 0.05). Both NMN and exercise interventions increased blood NAMPT concentrations, with the highest levels observed in the AENMN group (p < 0.05). SirT1 expression was elevated in the ASNMN and AENMN groups relative to YS (p < 0.05). Glucose tolerance improved in the ASNMN and AENMN groups (p < 0.05). Enhanced energy metabolism in the AENMN group was indicated by increased oxygen consumption, elevated energy expenditure, and reduced respiratory quotient. Conclusions: NMN supplementation, particularly when combined with aerobic exercise, effectively improved aerobic performance, glucose regulation, and systemic energy metabolism in aged mice. These findings suggest that NMN, in synergy with exercise, may serve as a promising nutritional strategy to counteract age-associated metabolic and functional decline. Full article

Polygonatum cyrtonema Hua, a plant with a long history of consumption in China, serves both medicinal and edible purposes, and it exhibits numerous pharmacological effects, including promoting kidney health and enhancing immune function. However, the effect and molecular mechanism of Polygonatum cyrtonema polysaccharides (PCPs) on hyperuricemia have not yet been reported. The hyperuricemic mice model was induced by the intraperitoneal injection of potassium oxonate (PO, 300 mg/kg), combined with the intragastric administration of hypoxanthine (HX, 300 mg/kg). Biochemical assays in mice revealed that PCPs markedly lowered high serum uric acid levels, suppressed xanthine oxidase (XOD) activity, and reduced the expression of inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Western blot analysis demonstrated that PCPs downregulated urate transporter 1 (URAT1), while H&E staining showed that PCPs effectively restored renal histological integrity. Here, we isolated and identified the PCPs, which consist mainly of rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose, with a molar mass ratio of 0.5:2.15:0.47:16.58:3.66:1.09. Furthermore, the galactose residue that docked with both XOD and URAT1 molecules forms more hydrogen bonds and exhibits a lower binding energy, which enables the improved regulation of both targets. We have demonstrated for the first time the improving effect of PCPs on hyperuricemia, and revealed their regulatory mechanisms by modulating xanthine oxidase, inflammatory factors, and uric acid transporters. This study not only provides new insights into the anti-hyperuricemic activity of PCPs in mice, but also lays a foundation for its potential application in the functional foods of anti-hyperuricemia. Full article

The zucchini market is growing worldwide due to its health and nutritional properties and culinary versatility. However, fruits harvested in the early stages of development are very perishable, which requires efforts to extend their shelf life. The aim of this study was to determine the effect of an innovative method involving a dynamically controlled atmosphere (DCA) and controlled atmosphere (CA) on the quality of zucchini stored at two temperatures (5 and 8 °C). After 20 d of cold storage, the fruit was further monitored under retail conditions (air, 15 °C). CA and DCA applied in a cold store at 8 °C improved the storage ability of the zucchini and allowed it to remain marketable for another 8 days at 15 °C. However, there were no significant effects of the storage method at 5 °C on the shelf life of zucchini at 15 °C. In addition, after storage at 8 °C under CA and DCA conditions, zucchini contained more total soluble solids (4.0%), glucose (8.0 g kg⁻¹), fructose (11.0 g kg⁻¹), and polyphenols (436 mg kg⁻¹) than those stored under normal atmosphere (3.6%, 6.2 g kg⁻¹, 9.9 g kg⁻¹, 377.8 mg kg⁻¹ respectively). The use of CA and DCA extends the shelf life and supports sustainable production and consumption of zucchini fruit. Full article

Background/Objectives: The consumption of highly palatable ultra-processed foods (UPFs), enriched in sugar, saturated fat, and salt, increases the risk of morbidity and mortality by inducing obesity, type 2 diabetes (T2DM), cardiovascular disease, and cancer. The present study aimed to investigate the impact of a UPF-rich diet on adiposity, feeding behavior, glucose homeostasis, intestinal barrier markers, expression of inflammatory cytokines, and microbiota in male and female C57BL/6J mice. Methods: Animals received a chow diet or a UPF diet for 10 (UPF10) or 30 days (UPF30). UPF10 induced greater calorie intake as early as 10 days on a UPF diet. Fat accumulation occurs in both sexes, specifically after 30 days of exposure. Results: The duration of UPF exposure significantly influenced glucose metabolism and insulin sensitivity. A 10-day UPF diet was associated with lower fasting blood glucose levels, without higher insulin levels, in both sexes. Females showed early impairment in glucose tolerance. Male mice on UPF30 exhibited elevated systemic IL-6 levels, as well as reduced intestinal expression of Occludin and E-cadherin genes. In females, UPF30 increased TNF-α expression in the gut and increased microbial diversity. Both sexes displayed dysbiosis, with females showing pronounced changes in the proportion between predominant phyla, and males showing more specific changes in bacterial genera. Conclusions: A diet high in UPFs promoted metabolic, inflammatory, and gut microbiota alterations, with effects varying according to exposure duration and biological context, and becoming more pronounced after 30 days. Full article

Background: Sweet taste adaptation, the decline in perceived sweetness with repeated exposure, may influence dietary behavior and differs across sweeteners. Low-calorie sweeteners (LCSs) such as sucralose strongly activate the T1R2+T1R3 receptor and are generally associated with greater adaptation than sugars, although this effect can be reduced with sweetener blends. Aim: We investigated whether habitual LCS consumption affects sweet taste perception and whether blending sucralose with small amounts of sugars attenuates adaptation using sensory tests in humans and in vivo calcium imaging in a rodent model. Methods: In study 1, habitual (HC; n = 39) and non-habitual (NHC; n = 42) LCS consumers rate sweetness of sucralose (0.6 mM), glucose (800 mM), fructose (475 mM), and blends with low glucose (111 mM) or fructose (45 mM) across repeated trials (1–10) using a generalized labeled magnitude scale. In study 2, a microfluidic-based intravital tongue imaging system was used to assess in vivo responses to sweet adaptation in genetically modified C57BL/6 mice (n = 8) expressing a calcium indicator in type II/III cells of taste buds. Results: Habitual LCS use was not associated with differences in sweetness perception or adaptation (all p-values > 0.6). Sucralose alone produced stronger adaptation than when blended with sugars in both humans (p-values < 0.002) and mice (p < 0.001). Glucose and fructose alone showed adaptation (relative decrease reached on final trial compared to the first trial: −27% ± 4% for glucose, −38% ± 5% for fructose, both p-values < 0.002) but to a lower degree compared with sucralose (−66% ± 5%). Conclusions: Sweetener composition, rather than habitual LCS use, drives sweet taste adaptation. Blending sucralose with small amounts of sugars reduces adaptation at both perceptual and cellular levels, providing mechanistic insights relevant to the formulation of LCS products. Full article

Background/Objectives: Poor glycemic control is reaching an epidemic prevalence globally. It is associated with significantly morbid health concerns including retinopathy, neuropathy, nephropathy, cancer, and cardiovascular disease. Probiotics have shown promise in reducing health complications associated with poor blood glucose control. We tested a novel approach to designing a precision probiotic cocktail for improving blood glucose homeostasis. Methods: We tested the in vitro glucose consumption rate of twelve mouse microbiome bacterial strains and selected three with the greatest glucose consumption for the probiotic cocktail. The in vivo metabolic impact of ingesting the selected probiotic cocktail was evaluated in twelve C57BL/6J male mice fed a high-fat diet for eight weeks. Results: Compared to a control group, the probiotic group (L. rhamnosus, L. reuteri, and L. salivarius) exhibited significantly lower blood glucose levels, body weight, and body fat percentage. Moreover, the probiotic cocktail also demonstrated the ability to reduce serum insulin, total cholesterol, very-low-density lipoprotein/low-density lipoprotein cholesterol, and total cholesterol to high-density lipoprotein ratio. For further mechanistic investigation, untargeted metabolomics analyses uncovered overall downregulations in energy substrates and producing pathways like gluconeogenesis, acylcarnitine synthesis, glycolysis, the mitochondrial electron transport chain, the TCA cycle, and the building blocks for ATP formation. Partial least squares-discriminant analyses also confirmed clear group differences in metabolic activity. 16S rRNA sequencing from extracted gut microbiota also showed significant increases in Faith’s phylogenetic diversity, Lachnospiraceae bacterium 609-strain, and the genus Muribaculaceae as well as group β-diversity differences after probiotic intake. Conclusions: As such, we successfully developed a blend of three probiotics to effectively reduce blood glucose levels in male mice, which could further mitigate adverse health effects in the host. Full article

Background/Objectives: Ethnopharmacological studies indicates that plant-based infusions are usually consumed by some people in advanced stages of diabetes, that is, when poor pancreatic dysfunction coexists with insulin resistance (IR). Current treatments aim to prevent β-cell deterioration by promoting improved insulin function and/or enhancing pancreatic function to avoid the development of hyperglycemia. Therefore, Croton guatemalensis (Cg) and Eryngium cymosum (Ec), two medicinal plants with potential insulin-sensitizing effects described in previous studies, were assessed on parameters related to IR and on the architecture of pancreatic islets in rats exposed to a syrup containing 8.8% glucose and 5.2% fructose in drinking water. Methods: After an 8-week exposure to syrup, plant extracts were orally administered for four weeks at traditional doses (Cg: 30 mg/kg body weight; Ec: 470 mg/kg body weight). Body weight, food intake, and drinking water consumption were monitored. At the end of the study, IR surrogate indices were calculated, metabolic assays were performed, and white adipose tissues, liver, gastrocnemius muscle, and pancreas were extracted in fasting and postprandial state for lipid quantification (liver), measurement of Akt phosphorylation status by western blot (liver and muscle), and determination of insulin content by immunohistochemistry (pancreatic islets). Results: Both species decreased hepatic lipid content without promoting significant changes in visceral adiposity. Although they did not improve surrogate markers of fasting IR, both ameliorated insulin function, glucose tolerance, and restored the glucose-stimulated insulin secretory response in metabolic tests. Cg restored the insulin signaling response in liver and muscle, whereas Ec only did so in muscle. Moreover, both appeared to enhance insulin pancreatic content or restore pancreatic islet population. Conclusions: Cg and Ec can reverse the IR phenotype in a tissue-specific manner and improve pancreatic function. Full article

There is an increasing industrial demand for sustainable resources for lipid-based biofuels and platform chemical production. A promising, CO₂-efficient resource is autotrophically cultivated microalgae, either for direct single-cell oil (SCO) production or as a biomass substrate for fermentative SCO production via organisms like yeasts. Regarding the latter, chemical biomass hydrolysis typically results in high sugar yield and high salt concentrations due to the required neutralization prior to fermentation. In contrast, enzymatic hydrolysis is often lacking in mass efficiency. In this study, the enzymatic hydrolysis of both nutrient-replete and lipid-rich autotrophic Microchloropsis salina biomass was optimized, testing different pre-treatments and enzyme activities. Hereby, the protease treatment to weaken the cell wall integrity and the dosing of the Cellic CTec3 was identified to have the highest effect on hydrolysis efficiency. Sugar yields of 63% (nutrient-replete) and almost 100% (lipid-rich) could be achieved. The process was successfully scaled-up in mini bioreactors at a 250 mL scale. The resulting hydrolysate of the lipid-rich biomass was tested as a substrate of the oleaginous yeast Cutaneotrichosporon oleaginosus in a consumption-based acetic acid fed-batch setup. It outperformed both the model substrate and the glucose control, demonstrating the high potential of the hydrolysate as feedstock for yeast oil production. The presented sequential and circular SCO-producing value chain highlights the potential for mass- and space–time-efficient biofuel production, combining the autotrophic cultivation of oleaginous algae with decoupled yeast oil fermentation for the first time. Full article

Growing evidence links processed red meat consumption to increased diabetes risk, with oxidized proteins and/or amino acids proposed as potential mediators. We investigated whether dityrosine (Dityr), a key oxidation biomarker in high-oxidative pork (HOP) and structural analog of thyroid hormone T3, mediates HOP-induced glucose dysregulation via thyroid hormone (TH) signaling disruption. C57BL/6J mice were fed control, low-oxidative pork (LOP), HOP, LOP + Dityr, or Dityr diets for 12 weeks. HOP and Dityr impaired glucose tolerance and induced hyperglycemia and hypoinsulinemia. Both induced oxidative stress and inflammation that partly contributed to pancreatic β-cell dysfunction and reduction in insulin secretion. Crucially, they downregulated pancreatic thyroid hormone receptor β1 (TRβ1) and monocarboxylate transporter 8 (MCT-8), impairing TH signaling. This reduced TH transport in pancreatic tissue and triggered β-cell apoptosis by modulating TRβ1-mediated expression of TH-responsive genes and proteins involved in pancreatic function, ultimately leading to diminished insulin secretion and elevated blood glucose levels. Dityr alone recapitulated the metabolic and molecular disruptions of HOP. We conclude that Dityr drives HOP-induced glucose metabolism disorders primarily by disrupting TH signaling, along with promoting oxidative stress and inflammation that collectively impair β-cell function. Minimizing dietary Dityr exposure via modified cooking methods or antioxidant-rich diets may mitigate diabetes risk. Full article

The surging demand for lithium-ion batteries (LIBs) has intensified the need for sustainable recovery of critical metals such as lithium, manganese, cobalt, and nickel from spent cathodes. While conventional hydrometallurgical and pyrometallurgical methods are widely used, they involve high energy consumption, hazardous waste generation, and complex processing steps, underscoring the urgency of developing eco-friendly alternatives. This study presents a novel, water-enhanced deep eutectic solvent (DES) system composed of choline chloride and D-glucose for the efficient leaching of valuable metals from spent LiMn-based battery cathodes. The DES was synthesized under mild conditions and applied to dissolve cathode powder, with leaching performance optimized by varying temperature and duration. Under optimal conditions (100 °C, 24 h), exceptional recovery efficiencies were achieved: 98.9% for lithium, 98.4% for manganese, and 71.7% for nickel. Material characterization using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and inductively coupled plasma mass spectrometer (ICP-MS) confirm effective phase dissolution and metal release. Although this DES system requires relatively higher temperature and longer reaction time compared to traditional acid leaching, it offers clear advantages in terms of non-toxicity, biodegradability, and elimination of strong oxidizing agents. These results demonstrate the potential of water-enhanced choline chloride–glucose DES as a green alternative for future development in sustainable battery recycling, supporting circular economy objectives. Full article

In this study, we constructed a recombinant Corynebacterium glutamicum strain for γ-aminobutyric acid (GABA) biosynthesis via the heterologous expression of glutamate decarboxylase (GAD) derived from Lactiplantibacillus plantarum. We systematically analyzed the fermentation strategy, the balance between cell growth and GAD expression, and the intracellular and extracellular glutamate and GABA levels during fermentation in recombinant C. glutamicum. The results demonstrated that a fermentation strategy combining variable-rate feeding with two-stage pH control at an initial glucose concentration of 50 g/L effectively enhanced cell proliferation, facilitated continuous glutamate synthesis and improved the catalytic efficiency of GAD. The intracellular and extracellular GABA synthesis improved up to 3.231 ± 0.024 g/L (a six-fold increase compared to the uncontrolled supplementation conditions). Furthermore, we fitted empirical equations relating cell growth, glucose consumption, GAD activity, and GABA synthesis during the fermentation. The maximum specific growth rate, glucose consumption rate, and GABA synthesis rate of recombinant C. glutamicum were 0.316 h⁻¹, 1.407 g/(g∙h), and 0.0697 g/L/h, respectively. The fermentation regulation strategy and the dynamic analysis of the fermentation process in this study provide support for future metabolic regulation strategies. Full article

Cherry consumption has been associated with several metabolic health benefits, due to their rich profile of bioactive compounds, including anthocyanins. This pilot clinical study, which is, to our knowledge, the first evaluating consumption of whole cherries, aimed to evaluate the effects of daily cherry consumption on oxidative stress, inflammation, glycaemic regulation, and other metabolic health markers in healthy adults. A total of 27 volunteers consumed 280 g of sweet cherries daily for 42 days, followed by a two-week post-intervention period. Significant improvements were observed in glucose regulation, including reduced HbA1c and estimated average glucose levels. Markers of inflammation, such as IL-6 and AGP-1 were significantly reduced during the intervention period. In addition, reductions in GGT and LDH indicated potential hepatoprotective effects. These results suggest that regular cherry consumption may serve as a preventive strategy against early metabolic dysfunction, highlighting the need for further investigation with larger, long-term clinical trials. Full article

Agricultural soils are hotspots of nitrous oxide (N₂O) emissions, where carbon substrates act as a critical factor influencing microbial community composition. However, how carbon availability modulates microbial denitrifying pathways and further influences N₂O emissions remains poorly understood. Here, we conducted anaerobic incubations to investigate North China vegetable soil N₂O production and consumption in response to varied glucose concentrations (0, 0.5 (Glu_0.5), 1.0 (Glu_1.0), and 2.0 (Glu_2.0) g C kg⁻¹ d.w. of soil). In this study, the δ¹⁵N^SP/δ¹⁸O mapping approach (δ¹⁵N^SP/δ¹⁸O MAP) and acetylene inhibition technique (AIT) were used to quantify the residual N₂O ratio (r_N2O) and the relative contributions of bacterial (f_BD) and fungal (f_FD) denitrification to N₂O production. The results showed that increasing glucose concentrations significantly increased CO₂ and N₂O emissions, with peak fluxes observed at Glu_2.0 on day 1 (116.22 ± 2.80 mg CO₂-C kg⁻¹ and 1.08 ± 0.02 mg N₂O-N kg⁻¹). Concurrently, δ¹⁵N^SP was also significantly elevated (p < 0.001), indicating enhanced f_FD, which was further corroborated by positive correlations between f_FD and glucose concentration (r = 0.48–0.56, p < 0.001). Nevertheless, bacterial denitrification (BD) still dominated N₂O production throughout the incubation period, except on day 1 in Glu_1.0 and Glu_2.0 of Case 2. Bland–Altman analysis with 95% limits of agreement (LoA) demonstrated strong agreement between the MAP and AIT in r_N2O estimation, particularly under Glu_2.0. All the above revealed glucose-induced denitrifying microbial shifts from BD to fungal denitrification (FD), which consequently modulated N₂O emissions and promoted incomplete denitrification. These findings collectively demonstrate that in vegetable cropping systems, rational carbon management strategies can promote N₂O reduction to N₂, thereby achieving effective N₂O mitigation. Full article