In order to improve the esterification efficiency of the enzymatic synthesis of l-ascorbic acid palmitate, the substrate analogue imprinting of the Aspergillus niger lipase-catalyzed esterification process was studied. Oleic acid was selected as the imprinting molecule, oleic acid imprinting immobilized lipase was prepared at pH 8.0, 0.1 g oleic acid, 1.5 mL of 95 % ethanol, and 0.1 g Tween-20. Through solubilization and supersaturation of Vitamin C, the reaction concentration of Vitamin C reached 5.00 % (m/v) in dioxane with 93.99 % esterification rate and 110.72 g/L of product concentration. Moreover, the Vitamin C reaction concentration can reach 8.00 % by using staged substrate feeding, and the esterification rate and product concentration of esterification after 28 h was 156.34 g/L and 82.96 %. Besides, the imprinting-induced conformational changes in enzyme proteins was characterized by fluorescence and infrared spectroscopy. This method provides a pathway for enzymatic production of l-ascorbic acid palmitate.

OBJECTIVE: There is no evidence on antioxidant-rich diets in preventing hypertension in heat-exposed workers. We aimed to evaluate the effects of formula supplemented with vitamin C (Vit C) and hawthorn beverage on reducing blood pressure (BP) and oxidative stress levels in heat-exposed workers.
METHODS: In the 40-day cluster-randomized controlled trial, four heat-exposed shift-teams were enrolled and randomly assigned to the intervention and control groups. The intervention group was given one Vit C tablet (130 mg) and a 500 mL hawthorn beverage containing 278.7 mg flavonoids daily whereas the control group was given 500 mL of slightly salted water daily; both groups were provided education on a healthy diet. BP and creatinine-corrected urinary 8-isoprostane-prostaglandin F2α (8-iso-PGF2α/Cr) concentrations were assessed at baseline, Day 17 (only BP) and Day 41, respectively.
RESULTS: Compared with the control group, the systolic BP (SBP), diastolic BP (DBP), and log10-transformed 8-iso-PGF2α/Cr in the inter-vention group decreased by 7.41 mmHg, 7.93 mmHg and 0.232, respectively, from baseline to day 41 (all p<0.05). When comparing BP levels at baseline, DBP in the intervention group was reduced by 5.46 mmHg when compared to control (p<0.05) among participants with lower baseline BP; SBP and DBP experienced reductions of 9.74 and 9.22 mmHg among participants with higher baseline BP (both p<0.05).
CONCLUSIONS: Supplementation of Vit C and flavonoids rich hawthorn beverage to heat-exposed workers prevented elevated BP caused by heat exposure which may be attributed to its oxidative stress inhibition effects.

BACKGROUND: Synchronous degradation between anthocyanin and vitamin C was found in fruit and vegetable juice matrices. To investigate whether the C-ring of anthocyanin is the key site of this interaction, cyanidin with four different C-ring modifications (3-glucosylation, 3,5-diglucosylation, 6″-malonylation, pyranylation) was added to vitamin C-containing apple juice, and the changes of anthocyanin retention, vitamin C retention, color, antioxidative activity and differential metabolites were analyzed.
RESULTS: The anthocyanin retention was in the order of pyranylation >6″-malonylation >3,5-diglucosylation >3-glucosylation. The vitamin C retention was in the order of 6″-malonylation > pyranylation >3,5-diglucosylation >3-glucosylation. The order of color stability was the same as that of anthocyanin retention, and the order of antioxidative activity was opposite to that of vitamin C retention. The results showed that modification at the C-ring limited the activity of anthocyanin, and suggested that the C-ring was one of the key sites for anthocyanin and vitamin C interaction. The shared differential metabolite of all apple juice matrices added with different anthocyanins was trans-hinokiresinol, which was likely generated from anthocyanin skeleton reacted with certain compounds in apple juice.
CONCLUSIONS: This study showed that modification of the anthocyanin C-ring could affect the anthocyanin and vitamin C interaction to some extent, which provided valuable insights for the application of anthocyanin C-ring modification in shelf-life quality control of typical fruit and vegetable beverages with the coexistence of anthocyanin and vitamin C. © 2024 Society of Chemical Industry.

This experiment was conducted to explore the effects of dietary vitamin C supplementation on non-specific immune defense, antioxidant capacity and resistance to low-temperature stress of juvenile mud crab (Scylla paramamosain). Mud crabs with an initial weight of 14.67 ± 0.13 g were randomly divided into 6 treatments and fed diets with 0.86 (control), 44.79, 98.45, 133.94, 186.36 and 364.28 mg/kg vitamin C, respectively. The experiment consisted of 6 treatments, each treatment was designed with 4 replicates and each replicate was stocked with 8 crabs. After 42 days of feeding experiment, 2 crabs were randomly selected from each replicate, and a total of 8 crabs in each treatment were carried out 72 h low-temperature challenge experiment. The results showed that crabs fed diets with 186.36 and 364.28 mg/kg vitamin C significantly improved the activities of alkaline phosphatase (AKP) and acid phosphatase (ACP) in hemolymph and hepatopancreas (P < 0.05). Crabs fed diet with 133.94 mg/kg vitamin C significantly decreased the concentration of nitric oxide (NO) and the activity of nitric oxide synthase (NOS) in hemolymph (P < 0.05). Diet with 133.94 mg/kg vitamin C was improved the activity of polyphenol oxidase (PPO) and the concentration of albumin (ALB) in hemolymph. Crabs fed diet with 133.94 mg/kg vitamin C showed lower concentration of malondialdehyde (MDA) in hemolymph and hepatopancreas than those fed the other diets. Meanwhile, crabs fed diet with 98.45 mg/kg vitamin C showed higher activity of total superoxide dismutase (T-SOD) in hemolymph, and crabs fed diet with 133.94 mg/kg vitamin C showed higher activity of T-SOD in hepatopancreas. Crabs fed diet with 186.36 mg/kg vitamin C significantly decreased the concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GSH-PX) in hepatopancreas (P < 0.05). In normal temperature, crabs fed diets with 133.94 mg/kg vitamin C significantly up-regulated the expression levels of gpx (glutathione peroxidase) and trx (thioredoxin) in hepatopancreas compared with the control treatment (P < 0.05). The highest expression levels of relish, il16 (interleukin 16), caspase 2 (caspase 2), p38 mapk (p38 mitogen-activated protein kinases) and bax (bcl-2 associated x protein) in hepatopancreas were found at crabs fed control diet (P < 0.05). Moreover, crabs fed diet with 133.94 mg/kg vitamin C showed higher expression levels of alf-3 (anti-lipopolysaccharide factor 3) and bcl-2 (B-cell lymphoma 2) in hepatopancreas than those fed the other diets (P < 0.05). Under low-temperature stress, crabs fed diet with 133.94 mg/kg vitamin C significantly improved the expression levels of hsp90 (heat shock protein 90), cat (catalase), gpx, prx (thioredoxin peroxidase) and trx in hepatopancreas (P < 0.05). In addition, dietary with 133.94 vitamin C significantly up-regulated the expression levels of alf-3 and bcl-2 (P < 0.05). Based on two slope broken-line regression analysis of activity of PPO against the dietary vitamin C level, the optimal dietary vitamin C requirement was estimated to be 144.81 mg/kg for juvenile mud crab. In conclusion, dietary 133.94-144.81 mg/kg vitamin C significantly improved the non-specific immune defense, antioxidant capacity and resistance to low-temperature stress of juvenile mud crab.

The use of cinnamaldehyde and Vitamin C can improve immunity and intestinal health. A two-way factorial design was employed to investigate the main and interactive effects of cinnamaldehyde and vitamin C on the growth, carcass, and intestinal health of broiler chickens. A total of 288 one-day-old female Arbor Acres broiler chicks were randomly distributed among four treatment groups, consisting of six replicate cages with 12 birds each. Four treatments were basal diet or control (CON), supplemental cinnamaldehyde (CA) 300 g/ton (g/t), vitamin C (VC) 300 g/t, and cinnamaldehyde 300 g/t, and vitamin C 300 g/t (CA + VC), respectively. The results showed that supplemental CA did not affect the growth performance or slaughter performance of broilers at 21 days (d), 42 days (d), and 1-42 days (d); however, it could improve intestinal barrier function at 42 d of age and reduce the mRNA expression of inflammatory factors in the intestine at 21 d and 42 d of age. Supplemental VC showed a trend towards increasing body weight gain (BWG) at 21 d (p = 0.094), increased breast muscle rate (at 21-d 5.33%, p < 0.05 and at 42-d 7.09%, p = 0.097), and decreased the abdominal fat (23.43%, p < 0.05) and drip loss (20.68%, p < 0.05) at 42-d. Moreover, VC improves intestinal morphology and intestinal barrier function and maintains a balanced immune response. The blend of CA and VC significantly upregulated the mRNA expression of myeloid differentiation factor 88 (MyD-88) in the intestine at 21 d of age, the mRNA expression of catalase (CAT), Occludin, Claudin-1, Mucin-2, nuclear factor-kappa B (NF-κB) and toll-like receptor 4 (TLR-4) in the intestine at 42 d of age (p < 0.01), and downregulated the mRNA expression of interleukin 10 (IL-10), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) in the intestine at 21-d and 42-d of age, and interleukin-1 beta (IL-1β) mRNA in intestine at 42 d of age (p < 0.01). This study suggested that the combination of CA and VC had the potential to regulate intestinal health and result in better carcass character of broilers.

OBJECTIVE: Both vitamin C and D deficiencies are extremely common in clinical practice, especially in elderly population. Unfortunately, the role of vitamin C deficiency in osteoporosis related consequences is often neglected. The aim of the present study is to analyse if combined vitamin C and D deficiency would have an association with bone mineral density (BMD) and osteoporotic vertebral fracture (OVF).
METHODS: Ninety-nine post-menopausal female patients admitted in the department of spine surgery of third affiliated hospital of Sun Yat-sen University were enrolled in the study. The participants were divided into four groups; vitamin D deficiency alone (comparator group), vitamin C deficiency alone and combined vitamin C and D deficiency as experimental group. The levels of vitamin C, vitamin D, calcium, phosphorous, BMD and condition of OVF were analysed.
RESULTS: There were statistically significant differences between the groups in terms of vitamin C and D levels. In terms of lumbar BMD, significant differences were observed between vitamin D deficiency alone and combined vitamin C and D deficiency. Only the combined vitamin C and D deficiency had a significant negative association with lumbar BMD and T-score. Similarly, combined vitamin C and D deficiency had a significant positive association with lumbar osteoporosis. None of the groups had any significant association with OVF. Combined vitamin C and D deficiency was found to be significantly associated with lower lumbar BMD and osteoporosis.
CONCLUSIONS: Combined vitamin C and D deficiency results in lower bone mineral density and higher risk of osteoporosis. We believe that existence of deficiencies of both vitamins could have a synergistic effect. Therefore, we recommend that vitamin C and D should be routinely measured in clinical practice.

Acute myeloid leukaemia (AML) is a heterogeneous disease characterized by complex molecular and cytogenetic abnormalities. Pro-oxidant cellular redox status is a common hallmark of AML cells, providing a rationale for redox-based anticancer strategy. We previously discovered that auranofin (AUF), initially used for the treatment of rheumatoid arthritis and repositioned for its anticancer activity, can synergize with a pharmacological concentration of vitamin C (VC) against breast cancer cell line models. In this study, we observed that this drug combination synergistically and efficiently killed cells of leukaemic cell lines established from different myeloid subtypes. In addition to an induced elevation of reactive oxygen species and ATP depletion, a rapid dephosphorylation of 4E-BP1 and p70S6K, together with a strong inhibition of protein synthesis were early events in response to AUF/VC treatment, suggesting their implication in AUF/VC-induced cytotoxicity. Importantly, a study on 22 primary AML specimens from various AML subtypes showed that AUF/VC combinations at pharmacologically achievable concentrations were effective to eradicate primary leukaemic CD34+ cells from the majority of these samples, while being less toxic to normal cord blood CD34+ cells. Our findings indicate that targeting the redox vulnerability of AML with AUF/VC combinations could present a potential anti-AML therapeutic approach.

BACKGROUND: In the treatment of advanced pancreatic cancer, chemotherapy plays a pivotal role. Despite its effectiveness, this regimen is often marred by side effects such as anemia, neuropathy, fatigue, nausea, and malnutrition, which significantly affect patients\' tolerance to the treatment. Some studies have shown that vitamin C could potentially augment chemotherapy\'s tolerability, notably by boosting iron absorption, ameliorating anemia, and relieving pain and numbness in hands and feet. Nevertheless, the integration of vitamin C with chemotherapy to mitigate toxic side effects and enhance the quality of life for advanced pancreatic cancer patients has not been examined in any randomized controlled trials to date.
METHODS: A prospective, single-center, open-label, randomized controlled trial will be conducted at Fudan University Shanghai Cancer Center from September 2023 to September 2026. A total of at least 100 patients with advanced pancreatic adenocarcinoma exhibiting distant metastases will be recruited and randomly assigned to the chemotherapy group or the chemotherapy plus vitamin C group. The primary endpoint is the rate of anemia. Secondary endpoints include the rate of grade 3 neuropathy, change of numeric rating scale, quality of life, and overall survival.
CONCLUSIONS: This study aims to assess the impact of low-dose vitamin C on enhancing the quality of life for patients with metastatic pancreatic cancer undergoing gemcitabine and nab-paclitaxel chemotherapy.
BACKGROUND: The trial was registered with the ClinicalTrials.gov (NCT06018883) on August 31, 2023.

Background: Exposure to heavy metals has been suggested to increase the risk of gestational diabetes mellitus (GDM) through the oxidative stress pathway. The study is aimed at examining whether vitamin C could modify the association between exposure to heavy metals and risk of GDM. Methods: We conducted a case-control study in Taiyuan, China, with 776 GDM cases and 776 controls. Data on vitamin C intake from diet and supplements were collected through questionnaires. Concentrations of metals in participants\' blood were measured using inductively coupled plasma-mass spectrometry (ICP-MS). Unconditional logistic regression models were applied to estimate effect modification of vitamin C on the association between heavy metals and GDM. Results: Women with higher blood levels of mercury (Hg) (odds ratio (OR) = 2.36, 95% confidence interval (CI): 1.43, 3.92 and 2.04, 95% CI: 1.20, 3.46 for the second and third vs. the first tertile) and arsenic (As) (OR = 2.46, 95% CI: 1.37, 4.43 and 2.16, 95% CI: 1.12, 4.17 for the second and third vs. the first tertile) exposure were associated with increased risk of GDM among women without vitamin C supplement use and having dietary vitamin C intake < 85 mg/day. We found no significant association with metals among women who took vitamin C supplements and/or dietary vitamin C ≥ 85 mg/day. Significant interactions were observed between vitamin C and exposures to metals (i.e., Hg and As) on the risk of GDM (P interaction = 0.048 and 0.045, respectively). Conclusions: Our study, for the first time, suggests that vitamin C supplement use or higher dietary vitamin C intake during preconception and early pregnancy could alleviate the risk of GDM associated with exposure to As and Hg. The results warrant further investigation.

Vitamin C (VC) serves as a pivotal nutrient for anti-oxidation process, metabolic responses, and stem cell differentiation. However, its precise contribution to placenta development and gestation remains obscure. Here, we demonstrated that physiological levels of VC act to stabilize Hand1, a key bHLH transcription factor vital for the development trajectory of trophoblast giant cell (TGC) lineages, thereby promoting the differentiation of trophoblast stem cells into TGC. Specifically, VC administration inactivated c-Jun N-terminal kinase (JNK) signaling, which directly phosphorylates Hand1 at Ser48, triggering the proteasomal degradation of Hand1. Conversely, a loss-of-function mutation at Ser48 on Hand1 not only significantly diminished both intrinsic and VC-induced stabilization of Hand1 but also underscored the indispensability of this residue. Noteworthy, the insufficiency of VC led to severe defects in the differentiation of diverse TGC subtypes and the formation of labyrinth\'s vascular network in rodent placentas, resulting in failure of maintenance of pregnancy. Importantly, VC deficiency, lentiviral knockdown of JNK or overexpression of Hand1 mutants in trophectoderm substantially affected the differentiation of primary and secondary TGC in E8.5 mouse placentas. Thus, these findings uncover the significance of JNK inactivation and consequential stabilization of Hand1 as a hitherto uncharacterized mechanism controlling VC-mediated placentation and perhaps maintenance of pregnancy.