Poly(ε-Caprolactone)-Based Composites Modified With Polymer-Grafted Magnetic Nanoparticles and L-Ascorbic Acid for Bone Tissue Engineering.

The aim of this study was to develop multifunctional magnetic poly(ε-caprolactone) (PCL) mats with antibacterial properties for bone tissue engineering and osteosarcoma prevention. To provide good dispersion of magnetic iron oxide nanoparticles (IONs), they were first grafted with PCL using a novel three-step approach. Then, a series of PCL-based mats containing a fixed amount of ION@PCL particles and an increasing content of ascorbic acid (AA) was prepared by electrospinning. AA is known for increasing osteoblast activity and suppressing osteosarcoma cells. Composites were characterized in terms of morphology, mechanical properties, hydrolytic stability, antibacterial performance, and biocompatibility. AA affected both the fiber diameter and the mechanical properties of the nanocomposites. All produced mats were nontoxic to rat bone marrow-derived mesenchymal cells; however, a composite with 5 wt.% of AA suppressed the initial proliferation of SAOS-2 osteoblast-like cells. Moreover, AA improved antibacterial properties against Staphylococcus aureus and Escherichia coli compared to PCL. Overall, these magnetic composites, reported for the very first time, can be used as scaffolds for both tissue regeneration and osteosarcoma prevention.

Molecular Dissection of the Arsenic-Induced Leukocyte Incursion into the Inflamed Thymus and Spleen and Its Amelioration by Co-supplementation of L-Ascorbic Acid and α-Tocopherol.

Arsenic, a surreptitious presence in our environment, perpetuates a persistent global menace with its deleterious impacts. It possesses the capability to trigger substantial immunosuppression by instigating inflammation in critical organs like the thymus and spleen. L-Ascorbic acid (L-AA) exhibits robust immunoregulatory prowess by orchestrating the epigenetic terrain through TET and JHDM pathways. Conversely, α-tocopherol (α-T) demonstrates the capacity to dampen the production of pro-inflammatory cytokines by modulating the PI3K-Akt axis. Given these insights, this inquiry embarks on exploring the mitigative potential of L-AA and α-T co-supplementation at the transcriptome level within leukocytes under arsenic exposure. Concurrently, the research endeavours to unravel the potent anti-inflammatory effects of administering α-T and L-AA, alleviating inflammation within the spleen and thymus amidst arsenic-induced insult and delving deeply into their immunomodulatory mechanisms. The rats were randomly allocated into eight distinct groups for subsequent experimentation: (I) the control group was administered solely with distilled water as the vehicle (control); (II) NaAsO2-treated group (As); (III) NaAsO2 treated along with L-ascorbic acid and α-tocopherol supplemented group (As + L-AA + α-T); (IV) L-ascorbic acid and α-tocopherol supplemented group (L-AA + α-T); (V) NaAsO2 treated along with L-ascorbic acid supplemented group (As + L-AA); (VI) only L-ascorbic acid supplemented group (L-AA); (VII) NaAsO2 treated along with α-tocopherol supplemented group (As + α-T); (VIII) only α-tocopherol supplemented group (α-T). Rats treated with NaAsO2 exhibited an increased neutrophil count in their bloodstream, as revealed by a comprehensive transcriptomic analysis showcasing heightened expressions of ItgaM, MMP9, and Itga4 within circulating leukocytes under arsenic exposure. Concurrently, arsenic heightened the expression of pro-inflammatory cytokines within the thymus and spleen. This elevated cytokine activity promoted the upregulation of ICAM-1 on vascular endothelial cells, facilitating the infiltration of Ly6g + leukocytes into the afflicted thymus and spleen. Remarkably, the combination of L-AA acid and α-T demonstrated substantial therapeutic efficacy, adeptly reducing the influx of Ly6g + leukocytes into these immune sites and subsequent reduction of excessive collagen deposition. The dynamic duo of L-AA and α-T achieved this amelioration by suppressing the expression of ItgaM, MMP9, and Itga4 mRNA within circulating leukocytes and moderating tissue levels of pro-inflammatory cytokines in arsenic-exposed thymus and spleen.

Development of Light-Scribing Process Using L-Ascorbic Acid for Graphene Micro-Supercapacitor.

The rapid development of smart technologies is accelerating the growing demand for microscale energy storage devices. This work reports a facile and practical approach to fabricating interdigitated graphene micro-patterns through the LSC process accompanied by the l-ascorbic acid (L-AA) and preheating treatment. Our work offered a higher degree of GO reduction than the conventional microfabrication. It significantly shortened the overall processing time to obtain the micro-patterns with improved electrical and electrochemical performances. The interdigitated MSC composed of 16 electrodes exhibited a high capacitance of 14.1 F/cm3, energy density of 1.78 mWh/cm3, and power density of 69.9 mW/cm3. Furthermore, the fabricated MSC device demonstrated excellent cycling stability of 88.2% after 10,000 GCD cycles and a high rate capability of 81.1% at a current density of 1.00 A/cm3. The fabrication process provides an effective means for producing high-performance MSCs for miniaturized electronic devices.

A systematic UHPLC Q-ToF MS approach for the characterization of bioactive compounds from freeze-dried red goji berries (L. barbarum L.) grown in Serbia: Phenolic compounds and phenylamides.

The aim of this study was to identify and characterise different classes of bioactive compounds from freeze-dried red goji berries (RGB) grown in Serbia, using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC Q-ToF MS). In addition, this study aims to demonstrate the importance of applying the advanced UHPLC Q-ToF MS technique in the identification of various biocompounds. The analysis showed the presence of 28 phenolic compounds, 3 organic acids, and 26 phenylamides. The 2-O-ß-d-glucopyranosyl-l-ascorbic acid (AA-2ßG) was identified by UHPLC Q-ToF MS and quantified by standardised UHPLC-DAD method. Most of the compounds detected were derivatives of caffeic acid and ferulic acid, followed by quercetin derivatives. Among the phenylamides, several glucosylated caffeoyl and/or dihydrocaffeoyl derivatives of spermidine and spermine were characterized, confirming their recent characterization. Some glycosylated/non-glycosylated putrescine derivatives and caffeoyl-dihydrocaffeoyl-feruloyl spermidines were identified in goji berriesfor the first time. Their tentative structures and fragmentations were proposed.

Effect of Rumen-Protected L-Tryptophan or L-Ascorbic Acid on Plasma Metabolites and Milk Production Characteristics of Lactating Holstein Cows during Summer Conditions.

This study investigated the effects of rumen-protected L-tryptophan or L-ascorbic acid supplementation on the productivity of lactating Holstein cows during a high-temperature period. Thirty cows were assigned to three dietary groups: control (CON), treatment 1 (TRT 1; rumen-protected L-tryptophan, 20 g/cow/d), and treatment 2 (TRT 2; rumen-protected L-ascorbic acid, 20 g/cow/d). As the high-temperature period progressed, the decrease in milk yield and dry matter intake (DMI) in the TRT 1 and TRT 2 groups was lower than that in the CON group. The total protein level in the plasma of the TRT 1 group was higher than that in the CON group (p < 0.05). Milk melatonin concentration was higher in the TRT 1 group than in the CON and TRT 2 groups (p < 0.05). Thus, the present results indicate that rumen-protected L-tryptophan or L-ascorbic acid has positive effects in preventing declines in DMI and milk yield by reducing heat stress in Holstein cows. In particular, rumen-protected L-tryptophan is considered effective in increasing the melatonin concentration in milk.

The evidence to date: implications of l-ascorbic acid in the pathophysiology of aging.

L-Ascorbic acid, commonly known as vitamin C, has been used not only for disease prevention and in complementary and alternative medicine, but also for anti-aging purposes. However, the scientific evidence is not yet sufficient. Here, we review the physiological functions of vitamin C and its relationship with various pathological conditions, including our previous findings, and discuss the prospects of its application in healthy longevity. In summary, vitamin C levels are associated with lifespan in several animal models. Furthermore, clinical studies have shown that the blood vitamin C levels are lower in middle-aged and older adults than in younger adults. Lower blood vitamin C levels have also been observed in various pathological conditions such as chronic kidney disease and chronic obstructive pulmonary disease in the elderly. These observations suggest the implications of vitamin C in age-related pathological mechanisms owing to its physiological functions.

EGCG induces degradation of active folate in serum via H2O2 generation, while L-ascorbic acid effectively reverses this effect.

Empirical studies have indicated that excessive tea consumption may potentially decrease folate levels within the human body. The main active component in green tea, epigallocatechin gallate (EGCG), significantly reduces the concentration of 5-methyltetrahydrofolate (5-MTHF) in both solution and serum. However, our findings also demonstrate that the pro-degradation effect of EGCG on 5-MTHF can be reversed by L-ascorbic acid (AA). Subsequent investigations suggest that EGCG could potentially expedite the degradation of 5-MTHF by generating hydrogen peroxide. In summary, excessive tea intake may lead to reduced folate levels in the bloodstream, yet timely supplementation of AA could potentially safeguard folate from degradation.

Comparative Assessment of Gingival Depigmentation Using Scalpel Versus Microneedling With Ascorbic Acid: A Randomized Controlled Trial.

Background Gingival pigmentation (GP), characterized by the presence of melanin in the gingival tissues, is a common aesthetic concern in dental practice. While it poses no inherent health risks, the visible discoloration may cause psychological distress for individuals seeking optimal dental aesthetics. Understanding the efficacy of various methods is essential for refining treatment strategies and enhancing patient satisfaction in the realm of gingival depigmentation (GD). Aim The objective of the study was to compare the effectiveness of scalpel and microneedling (MN) with ascorbic acid in the treatment of GD. Materials and methods Sixteen patients who had a complaint of GP were included in the study, of whom eight were allocated for depigmentation with a scalpel, and the other eight patients were treated with the MN technique with ascorbic acid. Postoperative wound healing scores were evaluated on the first and seventh days, respectively. The intensity of depigmentation was assessed at baseline, in the first month, and at the end of the third month, respectively. Results The mean Dummett-Gupta Oral Pigmentation Index (DOPI) score at baseline was 2.65±0.16 and 2.61±0.17 in the surgical and microneedling groups with ascorbic acid, respectively. The mean DOPI score at the end of the third month was 1.67±0.39 and 0.87±0.17 in the scalpel and MN with ascorbic acid groups, respectively. There was a statistically significant difference between the scalpel and MN with ascorbic acid groups at the end of the first and third months, respectively, where MN with ascorbic acid showed aesthetically pleasing outcomes. Patients treated with the scalpel technique showed incomplete healing and ulceration on the first and seventh days after the procedure when compared to the MN technique with ascorbic acid. The healing index scores were statistically significant in the MN with ascorbic acid group. Conclusion The MN technique with ascorbic acid is a successful technique for treating GD. It showed aesthetically gratifying outcomes when compared to the conventional surgical technique.

L-AP Alleviates Liver Injury in Septic Mice by Inhibiting Macrophage Activation via Suppressing NF-κB and NLRP3 Inflammasome/Caspase-1 Signal Pathways.

Liver injury and progressive liver failure are severe life-threatening complications in sepsis, further worsening the disease and leading to death. Macrophages and their mediated inflammatory cytokine storm are critical regulators in the occurrence and progression of liver injury in sepsis, for which effective treatments are still lacking. l-Ascorbic acid 6-palmitate (L-AP), a food additive, can inhibit neuroinflammation by modulating the phenotype of the microglia, but its pharmacological action in septic liver damage has not been fully explored. We aimed to investigate L-AP's antisepticemia action and the possible pharmacological mechanisms in attenuating septic liver damage by modulating macrophage function. We observed that L-AP treatment significantly increased survival in cecal ligation and puncture-induced WT mice and attenuated hepatic inflammatory injury, including the histopathology of the liver tissues, hepatocyte apoptosis, and the liver enzyme levels in plasma, which were comparable to NLRP3-deficiency in septic mice. L-AP supplementation significantly attenuated the excessive inflammatory response in hepatic tissues of septic mice in vivo and in cultured macrophages challenged by both LPS and ATP in vitro, by reducing the levels of NLRP3, pro-IL-1ß, and pro-IL-18 mRNA expression, as well as the levels of proteins for p-I-κB-α, p-NF-κB-p65, NLRP3, cleaved-caspase-1, IL-1ß, and IL-18. Additionally, it impaired the inflammasome ASC spot activation and reduced the inflammatory factor contents, including IL-1ß and IL-18 in plasma/cultured superannuants. It also prevented the infiltration/migration of macrophages and their M1-like inflammatory polarization while improving their M2-like polarization. Overall, our findings revealed that L-AP protected against sepsis by reducing macrophage activation and inflammatory cytokine production by suppressing their activation in NF-κB and NLRP3 inflammasome signal pathways in septic liver.

Design, synthesis, and biological evaluation of novel 2,3-Di-O-Aryl/Alkyl sulfonate derivatives of l-ascorbic acid: Efficient access to novel anticancer agents via in vitro screening, tubulin polymerization inhibition, molecular docking study and ADME predictions.

A series of novel l-ascorbic acid derivatives bearing aryl and alkyl sulfonate substituents were synthesized and characterized. In vitro anticancer evaluation against MCF-7 (breast) and A-549 (lung) cancer cell lines revealed potent activity for most of the compounds, with 2b being equipotent to the standard drug colchicine against MCF-7 (IC50 = 0.04 µM). Notably, compound 2b displayed 89-fold selectivity for MCF-7 breast cancer over MCF-10A normal breast cells. Derivatives with two sulfonate groups (2a-g, 3a-g) exhibited superior potency over those with one sulfonate (4a-c,5g, 6b). Compounds 2b and 2c potently inhibited tubulin polymerization in A-549 cancer cells (73.12 % and 62.09 % inhibition, respectively), substantiating their anticancer potential through microtubule disruption. Molecular docking studies showed higher binding scores and affinities for these compounds at the colchicine-binding site of α, ß-tubulin compared to colchicine itself. In-silico ADMET predictions indicated favourable drug-like properties, with 2b exhibiting the highest binding affinity. These sulfonate derivatives of l-ascorbic acid represents promising lead scaffolds for anticancer drug development.

Multifaceted Effects of L-Cysteine, L-Ascorbic Acid, and Their Derivatives on the Viability and Melanin Synthesis of B16/F10 Cells under Different Conditions.

The total melanin synthesis in the skin depends on various melanogenic factors, including the number of viable melanocytes, the level of melanogenic enzymes per cell, and the reaction rate of the enzymes. The purpose of this study is to examine the effects of L-cysteine (L-Cys), L-ascorbic acid (L-AA), and their derivatives on the tyrosinase (TYR) activity and autoxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) in vitro and the viability and melanin synthesis of B16/F10 cells under different conditions. L-Cysteinamide (C-NH2), glutathione (GSH), L-Cys, L-AA, and N-acetyl L-cysteine (NAC) inhibited the catalytic activity of TYR in vitro. L-AA, C-NH2, L-ascorbic acid 2-O-glucoside (AAG), and 3-O-ethyl L-ascorbic acid (EAA) inhibited the autoxidation of L-DOPA in vitro. L-DOPA exhibited cytotoxicity at 0.1 mM and higher concentrations, whereas L-tyrosine (L-Tyr) did not affect cell viability up to 3 mM. L-AA, magnesium L-ascorbyl 2-phosphate (MAP), and L-Cys attenuated the cell death induced by L-DOPA. C-NH2 decreased the intracellular melanin level at the basal state, whereas L-AA, MAP, and AAG conversely increased it. C-NH2 reduced the number of darkly pigmented cells via in situ L-DOPA staining, whereas L-AA, MAP, GSH, and AAG increased it. C-NH2 decreased the intracellular melanin level at the alpha-melanocyte-stimulating hormone (α-MSH)-stimulated state, while NAC and GSH increased it. L-AA and C-NH2 decreased the intracellular melanin level at the L-Tyr-stimulated state, but NAC and GSH increased it. L-Ascorbyl tetraisopalmitate (ATI) showed no or minor effects in most experiments. This study suggests that L-AA can either promote or inhibit the different melanogenic factors, and C-NH2 can inhibit the multiple melanogenic factors consistently. This study highlights the multifaceted properties of L-Cys, L-AA, and their derivatives that can direct their therapeutic applications in hyperpigmentation, hypopigmentation, or both disorders.

L-Ascorbic Acid Restricts Vibrio cholerae Survival in Various Growth Conditions.

Cholera, a deadly diarrheal disease, continues to ravage various parts of the world. It is caused by Vibrio cholerae, an important member of the gamma-proteobacteria. Based on certain genetic and phenotypic tests, the organism is classified into two major biotypes, namely classical and El Tor. The El Tor and its variants are majorly responsible for the ongoing seventh pandemic across the globe. Previously, we have shown that cross-feeding of glucose metabolic acidic by-products of gut commensals can severely affect the viability of the biotypes. In this work, we examined the effect of L-ascorbic acid on the survival of Vibrio cholerae strains belonging to both biotypes and different serotypes. We observed that L-ascorbic acid effectively restricts the growth of all strains under various conditions including strains adapted to acid stress. In addition, L-ascorbic acid is also effective in decreasing bile-induced biofilms of Vibrio cholerae.

The Vitamin C Enantiomers Possess a Comparable Potency in the Induction of Oxidative Stress in Cancer Cells but Differ in Their Toxicity.

The use of vitamin C (VC) in high doses demonstrates a potent tumor suppressive effect by mediating a glucose-dependent oxidative stress in Kirsten rat sarcoma (KRAS) mutant cancer cells. VC with arsenic trioxide (ATO) is a promising drug combination that might lead to the development of effective cancer therapeutics. Considering that a tumor suppressive effect of VC requires its high-dose administration, it is of interest to examine the toxicity of two enantiomers of VC (enantiomer d-optical isomer D-VC and natural l-optical isomer L-VC) in vitro and in vivo. We show that the combinations of L-VC with ATO and D-VC with ATO induced a similar cytotoxic oxidative stress in KrasG12D-expressing mutant cancer cells as indicated by a substantial increase in reactive oxidative species (ROS) production and depolarization of mitochondria. To examine the L-VC and D-VC toxicity effects, we administered high doses of D-VC and L-VC to CD1 mice and carried out an evaluation of their toxic effects. The daily injections of L-VC at a dose of 9.2 g/kg for 18 days were lethal to mice, while 80% of mice remained alive following the similar high-dose administration of D-VC. Following the drug injection courses and histopathological studies, we determined that a natural form of VC (L-VC) is more harmful and toxic to mice when compared to the effects caused by the similar doses of D-VC. Thus, our study indicates that the two enantiomers of VC have a similar potency in the induction of oxidative stress in cancer cells, but D-VC has a distinctive lower toxicity in mice compared to L-VC. While the mechanism of a distinctive toxicity between D-VC and L-VC is yet to be defined, our finding marks D-VC as a more preferable option compared to its natural enantiomer L-VC in clinical settings.

The volatile organic compounds generated from the Maillard reaction between l-ascorbic acid and l-cysteine in hot compressed water.

BACKGROUND: Hot compressed water (HCW), also known as subcritical water (SCW), refers to high-temperature compressed water in a special physical and chemical state. It is an emerging technology for natural product extraction. The volatile organic compounds (VOCs) generated from the Maillard reaction between l-ascorbic acid (ASA) and l-cysteine (Cys) have attracted significant interest in the flavor and fragrance industry. This study aimed to explore the formation mechanism of VOCs from ASA and Cys and examine the effects of reaction parameters such as temperature, time, and pH in HCW. RESULTS: The identified VOCs were predominantly thiophene derivatives, polysulfides, and pyrazine derivatives in HCW. The findings indicated that thiophene derivatives were formed under various pH conditions, with polysulfide formation favored under acidic conditions and pyrazine derivative formation preferred under weak alkaline conditions, specifically at pH 8.0. CONCLUSION: The Maillard reaction between ASA and Cys mainly produced thiophene derivatives, polysulfides, and pyrazine derivatives in HCW. The generation mechanism was significantly dependent on the surrounding pH conditions. © 2024 Society of Chemical Industry.

Structural insights into the Smirnoff-Wheeler pathway for vitamin C production in the Amazon fruit camu-camu.

l-Ascorbic acid (AsA, vitamin C) is a pivotal dietary nutrient with multifaceted importance in living organisms. In plants, the Smirnoff-Wheeler pathway is the primary route for AsA biosynthesis, and understanding the mechanistic details behind its component enzymes has implications for plant biology, nutritional science, and biotechnology. As part of an initiative to determine the structures of all six core enzymes of the pathway, the present study focuses on three of them in the model species Myrciaria dubia (camu-camu): GDP-d-mannose 3',5'-epimerase (GME), l-galactose dehydrogenase (l-GalDH), and l-galactono-1,4-lactone dehydrogenase (l-GalLDH). We provide insights into substrate and cofactor binding and the conformational changes they induce. The MdGME structure reveals a distorted substrate in the active site, pertinent to the catalytic mechanism. Mdl-GalDH shows that the way in which NAD+ association affects loop structure over the active site is not conserved when compared with its homologue in spinach. Finally, the structure of Mdl-GalLDH is described for the first time. This allows for the rationalization of previously identified residues which play important roles in the active site or in the formation of the covalent bond with FAD. In conclusion, this study enhances our understanding of AsA biosynthesis in plants, and the information provided should prove useful for biotechnological applications.

Enhanced Physical Stability of L-Ascorbic Acid in an Ionic Liquid.

Ionic liquid (IL) technology was used to enhance the stability of L-ascorbic acid (AA). Pyridoxine was selected as the counter cation for anionic AA in IL. After AA was dissolved in water at 40 °C, its ratio decreased to 3.2% after 7 d. In contrast, the IL formulation showed negligible degradation, with almost no loss of AA even after 28 d. These results suggest that the use of IL enhances the stability of AA.

Effects of quercetin and l-ascorbic acid on heterocyclic amines and advanced glycation end products production in roasted eel and lipid-mediated inhibition mechanism analysis.

Eel is a commercially important marine fish, frequently featured as sushi or roasted preparations. This study determined the formation of heterocyclic amines (HAs) and advanced glycation end products (AGEs) in roasted eel and evaluated the inhibitory mechanism of quercetin and l-ascorbic acid on their formation. The results indicate a respective reduction of 75.07% and 84.72% in total HAs, alongside a decline of 23.03% and 39.14% in AGEs. Additionally, fundamental parameters of roasted eel, lipid oxidation indicators and precursors were measured to elucidate the mechanisms and impact of natural antioxidants on HAs and AGEs formation in roasted eel. Furthermore, endeavors were made to probe into the molecular mechanisms governing the influence of key differential lipids on the generation of HAs and AGEs through lipid-mics analysis. This research emphasizes the potential of natural antioxidants in preventing harmful substances formation during eel thermal processing, which is helpful to food manufacturers for healthier food production.

Orange peel-derived carbon dots/Cu-MOF nanohybrid for fluorescence determination of l-ascorbic acid and Fe3.

Recycling and reuse of biomass waste in synthesis of nanomaterials have recently received much attention as an effective solution for environmental protection and sustainable development. Herein, nitrogen-doped carbon dots (N-CDs) with blue emission were synthesized from the orange peels as a precursor through a simple hydrothermal method and then, modified with ethylenediamine tetraacetic acid (N-CD@EDTA). The N-CD@EDTA was embedded as a fluorophore in Cu-based metal-organic framework (MOF-199) structure (N-CD@EDTA/MOF-199) to construct fluorescence sensor toward l-ascorbic acid (L-AA) determination. The N-CD@EDTA/MOF-199 nanohybrid significantly and selectively turned on toward L-AA determination during the fluorimetric experiments. Under optimal conditions, the probe showed a suitable linear response in the concentration range of 10 nM-100 µM with a low limit of detection (LOD) of 8.6 nM and high sensitivity of 0.201 µM-1. The possible mechanism of recognition and adsorption, including the reduction of Cu 2+ nodes in the MOF-199 structure in the presence of L-AA and the release of trapped N-CD@EDTA into the solution, was explored. Moreover, the N-CD@EDTA/MOF-199/L-AA (100 µM) system was further applied as a fluorescent "on-off" sensor for Fe3+ determination with a LOD of 1.15 µM. The proposed probe was successfully used in orange juice and water samples to determine L-AA and Fe3+ with satisfactory recovery, which displays the promising capability of sensor in real samples. The recoveries obtained by suggested method are consistent with that obtained from high performance liquid chromatography (HPLC) and atomic absorption spectroscopy which confirm the favorable characteristic of the sensor for accurate determination of L-AA and Fe3+ in practical applications.

Co-administration of L-Ascorbic Acid and α-Tocopherol Alleviates Arsenic-Induced Immunotoxicities in the Thymus and Spleen by Dwindling Oxidative Stress-Induced Inflammation.

Herein, we investigated whether L-ascorbic acid (L-AA) and α-tocopherol (α-T) co-administration has the potential to alleviate arsenic-induced immunotoxicities in the thymus, spleen, and circulating leukocytes. Forty-eight adult male Wistar rats were randomly divided into four groups before the treatment: group I (control); group II (sodium arsenite, 3 mg/kg/day/rat); group III (sodium arsenite + L-AA (200 mg/kg/day/rat) and α-T (400 mg/kg/day/rat)); group IV (L-AA and α-T). The result showed that sodium arsenite exposure (consecutive 30 days) caused weight reduction, structural alterations in the thymus and spleen, accompanied by a decrease in thymocyte and splenocyte count. Decreased superoxide dismutase and catalase activity, increased malondialdehyde and protein-carbonyl content, reduced Nrf2 and Bcl2 expression, and increased p-ERK, NF-kß, Bax, and cleaved-caspase-3 expression were also observed in the thymus and spleen of arsenic-exposed rats. Enhanced plasma ACTH and corticosterone, ROS-induced apoptosis of lymphocytes were also observed. L-AA and α-T co-administration has the potential to abrogate the deleterious impact of arsenic on the thymus, spleen, and circulating lymphocytes. Whole transcriptome analysis of leukocytes revealed that arsenic treatment augmented the expression of Itga4, Itgam, and MMP9 genes, which might help in transient migration of the leukocytes through the endothelial cell layer. Co-administration with L-AA and α-T maintained Itga4, Itgam, and MMP9 gene expression within leukocytes at a lower level.

Multicenter evaluation of a topical antioxidant serum.

BACKGROUND: A new antioxidant serum has been formulated with sodium ascorbate, a sodium salt of Vit C, which aims to address facial photodamage while maintaining a low irritation profile and preserving elastin. Detailed background science has been submitted in a previous publication. This open-label study was conducted to validate the science by demonstrating product efficacy and tolerability in patients with moderate to severe facial photodamage. METHODS: A multicenter, open-label clinical study was undertaken over 5 months from March 2023 to July 2023. Thirty six eligible participants (35 female, 1 male), aged 38-69 years, and Fitzpatrick skin types II-V were enrolled into and completed the study following 12 weeks of the topical antioxidant serum use twice daily, along with the following supporting products (gentle cleanser, moisturizer, and sunscreen for as needed use). Follow-up visits were conducted in Weeks 2, 4, 8, and 12. At every visit, participants were evaluated for facial photodamage severity and test product tolerability. Additionally, study participants underwent subject assessments and satisfaction questionnaires, investigator assessments, biopsy collection, and photography. RESULTS: Significant improvements in all evaluated facial photodamage parameters were observed at 12 weeks together with excellent tolerability and subject satisfaction persisting to Week 12 at study completion. Histology most notably revealed increased elastin fibers in 5 out of 5 post 12-week treatment biopsies on Movat staining, while Herovici stains revealed stimulation of collagen and early formation of new fibers. CONCLUSION: A novel antioxidant serum has demonstrated to be safe and effective for addressing facial photodamage, while stimulating the production of both elastin and collagen in the extracellular matrix (ECM).