Search Results (31)

This study aims to investigate the effects of dietary vitamin C supplementation on vitamin C synthesis, transport, and egg deposition in breeding geese. A total of 450 female and 90 male 221-day-old Yangzhou geese were randomly assigned to five treatment groups with six replicates each (15 females and 3 males per replicate). The control group received a basal diet, while the other four groups were fed diets supplemented with 100, 200, 300, and 400 mg/kg vitamin C over a 16-week feeding trial. The results showed that dietary vitamin C supplementation increased the vitamin C content in both serum and egg yolks and modulated the expression of key vitamin C-related genes. Specifically, the intestinal and ovarian sodium-dependent vitamin C transporters 1 and 2 (SVCT1/SVCT2) were upregulated, whereas hepatic and renal L-Gulonolactone oxidase (GLO) and SVCT1 were suppressed. These findings indicate that exogenous vitamin C enhances intestinal absorption, inhibits hepatic synthesis, and promotes yolk deposition, with 300 mg/kg emerging as an effective and practical supplementation level that provides a physiological basis for its application in poultry nutrition. Full article

Carbonic anhydrase 3 (CA3) exhibits low enzymatic activity compared to other CA isoforms but contains two surface-exposed cysteine residues that undergo glutathionylation under oxidative stress. Highly expressed in muscle tissue, CA3 has been implicated in cellular protection, particularly through interactions with Bcl2-Associated Athanogene 3 (BAG3), modulating autophagy, while CA3 overexpression decreased hypoxia-induced apoptosis in cardiomyocytes. In this study, we investigated the impact of CA3 overexpression on cellular pathways in HEK293T, MDA-MB-231, and SVCT cells using RNA sequencing and proteomics. Gene Set Enrichment Analysis (GSEA) in HEK293T cells revealed the down-regulation of pathways related to protein synthesis, RNA processing, Roundabout signalling, selenocysteine-metabolism, and suppression of neurodegenerative disease-associated pathways. Human breast epithelial cell lines under normoxia and hypoxia showed down-regulation of similar pathways, although notably, hypoxic conditions also suppressed interferon α/β signalling. Proteomic analysis in HEK293T cells using HaloTag pull-down experiments identified putative novel CA3 binding partners, including heat shock 70 kDa proteins 1 and 8, and ribosomal protein S2 (RPS2). RANBP2 protein was consistently up-regulated after CA3 overexpression, irrespective of the presence of CA3 surface-exposed cysteines and HaloTag orientation. These findings suggest that CA3 modulates key cellular processes beyond its enzymatic role, contributing to stress resilience through pathway-level regulation and protein interactions, potentially impacting autophagy and neurodegenerative disease. Full article

Fine particulate matter (PM2.5) emitted by wood smoke is a significant environmental pollutant associated with oxidative stress and hypoxia. These conditions can disrupt placental function by altering the expression of key nutrient transporters, such as glucose transporter 1 (GLUT1) and sodium-dependent vitamin C transporter 2 (SVCT2), which are essential for fetal development. This study evaluates the effects of pregestational and gestational exposure to PM2.5 on GLUT1 and SVCT2 expression in the rat placenta. Pregnant Sprague–Dawley rats were exposed to either filtered air (FA) or non-filtered air (NFA) containing PM2.5 from wood combustion in a controlled exposure system. Four experimental groups were established: FA/FA (control), FA/NFA (gestational exposure), NFA/FA (pregestational exposure), and NFA/NFA (continuous exposure). Immunofluorescence and confocal microscopy were used to quantify the expression of GLUT1 and SVCT2 in the placental labyrinth zone. Statistical analyses were performed using Kruskal–Wallis and post hoc Dunn’s test (p < 0.05). Gestational exposure to PM2.5 (FA/NFA) significantly reduced GLUT1 and SVCT2 expression, compromising glucose transport and antioxidant protection in the placenta. Pregestational exposure (NFA/FA) induced a compensatory increase in SVCT2 expression, suggesting an adaptive response to oxidative stress. Continuous exposure (NFA/NFA) resulted in GLUT1 redistribution within the syncytiotrophoblast and decreased membrane localization, potentially impairing glucose uptake. PM2.5 exposure disrupts the expression and localization of GLUT1 and SVCT2 in the placenta, with differential effects depending on the timing of exposure. The gestational phase appears to be particularly vulnerable, as reduced GLUT1 and SVCT2 levels may impair fetal nutrition and antioxidant defense. These findings underscore the need for preventive measures to mitigate air pollution-related risks during pregnancy. Full article

Vitamin C, also known as L-ascorbic acid (AA), functions as a pro-oxidant in cancer at high doses and exerts anticancer effects by generating reactive oxygen species (ROS) and selectively inducing damage to cancer cells. However, AA at low doses promotes cancer cell proliferation. The efficacy of high-dose AA therapy is frequently restricted by inadequate intracellular AA uptake, resulting from low expression of sodium-dependent vitamin C transporter 2 (SVCT2). In this study, we investigated whether valproic acid (VPA), a histone deacetylase inhibitor, could circumvent this constraint by increasing the expression of SVCT2 in colorectal cancer cells, including HCT-116 and DLD-1 with low SVCT2 levels. We found that VPA increased SVCT2 expression in both cell lines. Co-treatment with AA and VPA increased the number of apoptotic cells and enhanced intracellular AA uptake via VPA-upregulated SVCT2, followed by increased ROS production in both cell lines. Furthermore, the combination increased the synergistic anticancer effects and suppressed the hormetic dose response of AA in both cell lines. In a xenograft mouse model, co-treatment decreased tumor size and increased the tumor growth inhibition ratio compared to treatment with AA or VPA alone. Accordingly, VPA treatment enhanced SVCT2 expression in colorectal cancer cells, suppressed the hormetic dose-response effect of AA, and improved the potential of high-dose AA therapy as an anticancer agent. Full article

Reactive oxygen species (ROS) contribute to cerebral damage in transient cerebral ischemia, making their elimination a key therapeutic target. Osteogenic disorder Shionogi (ODS) rats, which lack endogenous L-ascorbic acid (AA) synthesis, serve as a useful model for investigating AA’s protective effects against ischemic brain injury. ODS rats were given an AA-free diet (0% AA), 0.1% AA, or 1% AA in drinking water for two weeks before undergoing middle cerebral artery occlusion and reperfusion (MCAO/Re). The 0% AA group exhibited pronounced damage following MCAO/Re, characterized by the induction of lipid peroxidation, O₂⁻ production, inflammation-related gene expression, and extensive infarct formation. In contrast, the 1% AA group showed reductions in these markers, along with fewer TUNEL-positive cells and a smaller infarct volume. Notably, sodium-dependent vitamin C transporter 2 (SVCT2) expression increased in both two AA-supplemented groups, although the 0.1% AA group did not exhibit sufficient improvement in post-ischemic damage. A two-week intake of AA significantly alleviated MCAO/Re-mediated injuries associated with oxidative stress and inflammation in ODS rats. Sufficient AA intake is thus supposed to mitigate ischemic damage, possibly through SVCT2 upregulation and enhanced AA availability, leading to the suppression of oxidative stress and inflammation. Full article

Background/Objectives: Vitamin C is a well-known antioxidant with antiviral, anticancer, and anti-inflammatory properties. However, its therapeutic applications are limited by rapid oxidation due to heat and light sensitivity. Aptamin C, which employs aptamers to bind vitamin C, has demonstrated enhanced stability and efficacy. This study investigates the potential of Aptamin C to inhibit the progression of pulmonary fibrosis, a prominent inflammatory lung disease with no effective treatment. Methods: Mice bearing bleomycin-induced pulmonary fibrosis were administered vitamin C or Aptamin C, and their weight changes and survival rates were monitored. Inflammatory cell infiltration was assessed in the bronchoalveolar lavage fluid (BALF), and the degree of alveolar fibrosis was measured by H&E and Masson’s trichrome staining. To elucidate the mechanism of action of Aptamin C, Western blot analysis was performed in HaCaT and lung tissues from bleomycin-induced pulmonary fibrosis mice. Results: The Aptamin C-treated group showed a notably higher survival rate at 50%, whereas all subjects in the vitamin C-treated group died. Histological examination of lung tissue showed that inflammation was significantly suppressed in the Aptamin C-supplemented group compared to the vitamin C-supplemented group, with a 10% greater reduction in cell infiltrations, along with noticeably less tissue damage. Additionally, it was observed that Aptamin C increased SVCT-1 expression in the HaCaT cells and the lung tissues. Conclusions: Taken together, Aptamin C not only increases the stability of vitamin C but also induces an increase in SVCT-1 expression, facilitating greater vitamin C absorption into cells and tissues, thereby inhibiting the progression of symptoms and associated inflammatory responses in pulmonary fibrosis. Full article

The role of food constituents as pharmacological agents is an important consideration in health and obesity. Vitamin C acts as a small molecule antioxidant but is also a co-factor for numerous transition metal-dependent enzymes involved in healthy weight and energy metabolism. Vitamin C cannot be manufactured by humans and is mainly obtained from the dietary intake of fresh fruit and vegetables. There is great variability between different nutritional guidelines in the recommended daily allowance of vitamin C. Vitamin C deficiency results from an inadequate intake of vitamin C-containing foods and also increased utilization by oxidative and carbonyl stress. Risk factors for vitamin C deficiency include cigarette smoking, malnutrition, obesity, type 2 diabetes mellitus, age, race, sex, social isolation, major surgery, and Western-type diets. Despite the common belief that vitamin C deficiency is rare in affluent countries, surveys of large populations and specific patient groups suggest otherwise. Patients with obesity typically consume highly processed, energy-dense foods which contain inadequate micronutrients. As obesity increases, larger amounts of oral vitamin C are required to achieve adequate plasma and tissue concentrations, as compared to persons with a healthy weight. This is important in the control of oxidative stress and the maintenance of homeostasis and organ function. In this narrative review, the dosage, absorption, distribution, excretion, and catabolism of vitamin C are reviewed, together with the latest findings on vitamin C pharmacology in patients with obesity. Full article

Sparse view computed tomography (SVCT) aims to reduce the number of X-ray projection views required for reconstructing the cross-sectional image of an object. While SVCT significantly reduces X-ray radiation dose and speeds up scanning, insufficient projection data give rise to issues such as severe streak artifacts and blurring in reconstructed images, thereby impacting the diagnostic accuracy of CT detection. To address this challenge, a dual-domain reconstruction network incorporating multi-level wavelet transform and recurrent convolution is proposed in this paper. The dual-domain network is composed of a sinogram domain network (SDN) and an image domain network (IDN). Multi-level wavelet transform is employed in both IDN and SDN to decompose sinograms and CT images into distinct frequency components, which are then processed through separate network branches to recover detailed information within their respective frequency bands. To capture global textures, artifacts, and shallow features in sinograms and CT images, a recurrent convolution unit (RCU) based on convolutional long and short-term memory (Conv-LSTM) is designed, which can model their long-range dependencies through recurrent calculation. Additionally, a self-attention-based multi-level frequency feature normalization fusion (MFNF) block is proposed to assist in recovering high-frequency components by aggregating low-frequency components. Finally, an edge loss function based on the Laplacian of Gaussian (LoG) is designed as the regularization term for enhancing the recovery of high-frequency edge structures. The experimental results demonstrate the effectiveness of our approach in reducing artifacts and enhancing the reconstruction of intricate structural details across various sparse views and noise levels. Our method excels in both performance and robustness, as evidenced by its superior outcomes in numerous qualitative and quantitative assessments, surpassing contemporary state-of-the-art CNNs or Transformer-based reconstruction methods. Full article

Acute respiratory distress syndrome (ARDS) is a life-threatening event that occurs in patients suffering from bacterial, fungal, or viral sepsis. Research performed over the last five decades showed that ARDS is a consequence of severe unrestrained systemic inflammation, which leads to injury of the lung’s microvasculature and alveolar epithelium. ARDS leads to acute hypoxic/hypercapnic respiratory failure and death in a significant number of patients hospitalized in intensive care units worldwide. Basic and clinical research performed during the time since ARDS was first described has been unable to construct a pharmacological agent that will combat the inflammatory fire leading to ARDS. In-depth studies of the molecular pharmacology of vitamin C indicate that it can serve as a potent anti-inflammatory agent capable of attenuating the pathobiological events that lead to acute injury of the lungs and other body organs. This analysis of vitamin C’s role in the treatment of ARDS includes a focused systematic review of the literature relevant to the molecular physiology of vitamin C and to the past performance of clinical trials using the agent. Full article

Ascorbate plays a vital role as a co-factor for a superfamily of enzymes, the 2-oxoglutarate dependent dioxygenases (2-OGDDs), which govern numerous pathways in cancer progression, including the hypoxic response and the epigenetic regulation of gene transcription. Ascorbate uptake into most cells is through active transport by the sodium-dependent vitamin C transporter 2 (SVCT2). The aims of this study were to determine the kinetics of ascorbate uptake and retention by breast cancer cell lines under various oxygen conditions, and to investigate the role of SVCT2 in mediating ascorbate uptake and intracellular trafficking. Human MDA-MB231 cells accumulated up to 5.1 nmol ascorbate/10⁶ cells, human MCF7 cells 4.5 nmol/10⁶ cells, and murine EO771 cells 26.7 nmol/10⁶ cells. Intracellular ascorbate concentrations decreased rapidly after reaching maximum levels unless further ascorbate was supplied to the medium, and there was no difference in the rate of ascorbate loss under normoxia or hypoxia. SVCT2 was localised mainly to subcellular compartments, with the nucleus apparently containing the most SVCT2 protein, followed by the mitochondria. Much less SVCT2 staining was observed on the plasma membrane. Our data showed that careful management of the doses and incubation times with ascorbate in vitro allows for an approximation of in vivo conditions. The localisation of SVCT2 suggests that the distribution of ascorbate to intracellular compartments is closely aligned to the known function of ascorbate in supporting 2-OGDD enzymatic functions in the organelles and with supporting antioxidant protection in the mitochondria. Full article

The problem of sparse-view computed tomography (SVCT) reconstruction has become a popular research issue because of its significant capacity for radiation dose reduction. However, the reconstructed images often contain serious artifacts and noise from under-sampled projection data. Although the good results achieved by the prior image constrained compressed sensing (PICCS) method, there may be some unsatisfactory results in the reconstructed images because of the image gradient L₁-norm used in the original PICCS model, which leads to the image suffering from step artifacts and over-smoothing of the edge as a result. To address the above-mentioned problem, this paper proposes a novel improved PICCS algorithm (NPICCS) for SVCT reconstruction. The proposed algorithm utilizes the advantages of PICCS, which could recover more details. Moreover, the algorithm introduces the L₀-norm of image gradient regularization into the framework, which overcomes the disadvantage of conventional PICCS, and enhances the capability to retain edge and fine image detail. The split Bregman method has been used to resolve the proposed mathematical model. To verify the effectiveness of the proposed method, a large number of experiments with different angles are conducted. Final experimental results show that the proposed algorithm has advantages in edge preservation, noise suppression, and image detail recovery. Full article

Ascorbic acid (AA) is an indispensable nutrient required to sustain optimal poultry health and performance, which is commonly excluded from the diet of broilers. To investigate the synthesis and distribution of AA during broiler growth and clarify its possible turnover, 144 1 d old healthy Arbor Acres broilers with a body weight of approximately 41 g were randomly assigned to eight groups of 18 broilers each. The kidney, liver, ileum, and spleen of one bird from each group were collected every week until 42 d to detect the synthesis capacity, tissue distribution, and transporter gene expression of AA. The results showed that kidney L-gulonolactone oxidase (GLO) activity responded quadratically (p < 0.001), with maximum activity observed at 7 to 21 d old. Hepatic total AA and dehydroascrobate (DHA) concentration increased linearly (p < 0.001) with age, as did splenic total AA (p < 0.001). In the ileum, mRNA expression of sodium vitamin C transporter 1/2 (SVCT1/2) decreased with the growing age of the broilers (p < 0.05). The expression of SVCT1 in the kidney was not influenced by the growing age of the broilers. The progressive buildup of AA in the liver and spleen of broilers as they age implies an amplified demand for this nutrient. The waning synthesis capacity over time, however, raises concerns regarding the possible inadequacy of AA in the latter growth phase of broilers. The addition of AA to the broilers’ diet might have the potential to optimize their performance. However, the effectiveness of such dietary supplementation requires further investigation. Full article

Targeted monoclonal antibody therapy against Epidermal Growth Factor Receptor (EGFR) is a leading treatment modality against metastatic colorectal cancer (mCRC). However, with the emergence of KRAS and BRAF mutations, resistance was inevitable. Cells harboring these mutations overexpress Glucose Transporter 1 (GLUT1) and sodium-dependent vitamin C transporter 2 (SVCT2), which enables intracellular vitamin C transport, leading to reactive oxygen species generation and finally cell death. Therefore, high dose vitamin C is proposed to overcome this resistance. A comprehensive search strategy was adopted using Pubmed and MEDLINE databases (up to 11 August 2022). There are not enough randomized clinical trials to support its use in the clinical management of mCRC, except for a subgroup analysis from a phase III study. High dose vitamin C shows a promising role in overcoming EGFR resistance in mCRC with wild KRAS mutation with resistance to anti-epidermal growth factor inhibitors and in patients with KRAS and BRAF mutations. Full article

Ascorbate (vitamin C in primates) functions as a cofactor for a number of enzymatic reactions represented by prolyl hydroxylases and as an antioxidant due to its ability to donate electrons, which is mostly accomplished through non-enzymatic reaction in mammals. Ascorbate directly reacts with radical species and is converted to ascorbyl radical followed by dehydroascorbate. Ambiguities in physiological relevance of ascorbate observed during in vivo situations could be attributed in part to presence of other redox systems and the pro-oxidant properties of ascorbate. Most mammals are able to synthesize ascorbate from glucose, which is also considered to be an obstacle to verify its action. In addition to animals with natural deficiency in the ascorbate synthesis, such as guinea pigs and ODS rats, three strains of mice with genetic removal of the responsive genes (GULO, RGN, or AKR1A) for the ascorbate synthesis have been established and are being used to investigate the physiological roles of ascorbate. Studies using these mice, along with ascorbate transporter (SVCT)-deficient mice, largely support its ability in protection against oxidative insults. While combined actions of ascorbate in regulating epigenetics and antioxidation appear to effectively prevent cancer development, pharmacological doses of ascorbate and dehydroascorbate may exert tumoricidal activity through redox-dependent mechanisms. Full article

Ascorbate is an important element of a variety of cellular processes including the control of reactive oxygen species levels. Since reactive oxygen species are implicated as a key factor in tumorigenesis and antitumor therapy, the injection of a large amount of ascorbate is considered beneficial in cancer therapy. Recent studies have shown that ascorbate can cross the plasma membrane through passive diffusion. In contrast to absorption by active transport, which is facilitated by transport proteins (SVCT1 and SVCT2). The passive diffusion of a weak acid across membranes depends on the electrostatic potential and the pH gradients. This has been used to construct a new theoretical model capable of providing steady-state ascorbate concentration in the intracellular space and evaluating the time needed to reach it. The main conclusion of the analysis is that the steady-state intracellular ascorbate concentration weakly depends on its serum concentration but requires days of exposure to saturate. Based on these findings, it can be hypothesized that extended oral ascorbate delivery is possibly more effective than a short intravenous infusion of high ascorbate quantities. Full article