Therapeutic effects of high-dose vitamin C supplementation in patients with COVID-19: a meta-analysis.

CONTEXT: Coronavirus disease 2019 (COVID-19) could induce the "cytokine storm" due to overactivation of immune system and accompanied by acute respiratory distress syndrome as a serious complication. Vitamin C has been effective in improving lung function of patients by reducing inflammation. OBJECTIVE: The aim was to explore the therapeutic effects of high-dose vitamin C supplementation for patients with COVID-19 using meta-analysis. DATA SOURCES: Published studies were searched from PubMed, Cochrane Library, Web of Science, EMBASE, and China National Knowledge Infrastructure databases up to August 2022 using the terms "vitamin C" and "COVID-19". Data analyses were performed independently by 2 researchers using the PRISMA guidelines. DATA EXTRACTION: Heterogeneity between the included studies was assessed using I2 statistics. When I2 ≥50%, the random-effects model was used; otherwise, a fixed-effects model was applied. Stata 14.0 software was used to pool data by standardized mean differences (SMDs) with 95% CIs or odds ratios (ORs) with 95% CIs. DATA ANALYSIS: The 14 studies had a total of 751 patients and 1583 control participants in 7 randomized controlled trials and 7 retrospective studies. The vitamin C supplement significantly increased ferritin (SMD = 0.272; 95% CI: 0.059 to 0.485; P = 0.012) and lymphocyte count levels (SMD = 0.376; 95% CI: 0.153 to 0.599; P = 0.001) in patients with COVID-19. Patients administered vitamin C in the length of intensive care unit staying (SMD = 0.226; 95% CI: 0.073 to 0.379; P = 0.004). Intake of vitamin C prominently alleviate disease aggravation (OR = 0.344, 95%CI: 0.135 to 0.873, P = 0.025). CONCLUSIONS: High-dose vitamin C supplementation can alleviate inflammatory response and hinder the aggravation of COVID-19.

A facile one step solvothermal controllable synthesis of FeS2 quantum dots with multiple color emission for the visual detection of aconitine.

Iron disulfide (FeS2) quantum dots have potential applications in various fields such as photocatalysis, lithium-ion batteries and bioimaging. At present, there is no report on the fluorescent characteristics of FeS2 quantum dots (FeS2 QDs). In this work, a synthesis of multiple-color emission FeS2 QDs by changing the temperature, time and raw ratio has been reported. The blue, green, yellow and red emission FeS2 QDs can be obtained, respectively. They were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and transmission electron microscope (TEM). On this basis, a novel molecular imprinting ratiometric fluorescence sensor (MIR sensor) had been constructed, in which the blue-emission FeS2 QDs (b-FeS2 QDs) was used as a fluorescent responsive signal material and the yellow-emission FeS2 QDs (y-FeS2 QDs) was served as a reference signal material. And this MIR sensor was applied for highly selective and sensitive detection of ACO in traditional Chinese medicine (TCM). Under the optimum conditions, the MIR sensor exhibited an excellent linear relationship between the fluorescence intensity ratio (I443/I590) and the concentration of ACO in the range of 0.05-5.0 µM with a detection limit of 24 nM. Furthermore, the established method was successfully utilized to the detection of ACO in TCM Fuzi Lizhong Pills with satisfactory results. It provided a reference for the application of the FeS2 QDs with multiple color emission and the detection of the hazardous alkaloids.

Assessment of nephrotoxicity of herbal medicine containing aristolochic acid in mice.

BACKGROUND/AIMS: It is undetermined if herbal medicines (HM) containing aristolochic acid (AA)-containing have similar nephrotoxicity to AA itself. METHODS: We administered HM containing a high concentration of AA for 5 days (short-term study) or a low concentration of AA for 30 days (long-term study) to C57BL/6 mice; for comparison, same dose of AA compound was used as controls. RESULTS: The nephrotoxicity in the HM- and AA-treated mice was compared in terms of renal function, histopathology, oxidative stress, apoptotic cell death, and mitochondrial damage. Short-term HM treatment resulted in acute kidney injury (marked renal dysfunction, acute tubular necrosis, and neutrophil gelatinase-associated lipocalin [NGAL] expression) in which the severity of renal dysfunction and histopathology was comparable with that induced by the administration of AA alone. Long-term HM treatment resulted in features of chronic kidney disease (CKD, mild renal dysfunction and tubular atrophy and dilatation). No significant differences in these parameters were observed between the HM- and AA-treated mice. HM-induced oxidative stress (8-hydroxy-2'-deoxyguanosine and manganese- dependent superoxide dismutase expression) and apoptotic cell death (terminal deoxynucleotidyl transferase dUTP nick end labelling [TUNEL]-positive cells and active caspase-3 expression) were similar in HM- and AA-treated mice in the short-term and long-term studies. Mitochondrial injury, evaluated by electron microscopy, was also similar in HM- and AA-treated mice in the short-term and long-term studies. CONCLUSION: The nephrotoxic potential of HM containing AA was similar to that of AA itself.

Coenzyme Q10 alleviates tacrolimus-induced mitochondrial dysfunction in kidney.

The major side effect of tacrolimus (Tac) is nephrotoxicity. We studied whether supplementation of coenzyme Q10, (CoQ10) a potent antioxidant, can reduce Tac-induced nephrotoxicity via improving mitochondrial function. In an in vitro study, CoQ10 reduced the production of Tac-induced mitochondrial reactive oxygen species and abolished the loss of mitochondrial membrane potential in proximal tubular cell line. Assessment of mitochondrial function revealed that CoQ10 decreased oxygen consumption and mitochondrial respiration rate increased by Tac, suggesting improvement of mitochondrial function to synthesize ATP with CoQ10 treatment. The effect of the CoQ10in vitro study was observed in an experimental model of chronic Tac-induced nephropathy. CoQ10 attenuated Tac-induced oxidative stress and was accompanied by function and histologic improvement. On electron microscopy, addition of CoQ10 increased not only the number but also the volume of mitochondria compared with Tac treatment only. Our data indicate that CoQ10 improves Tac-induced mitochondrial dysfunction in kidney. Supplementary CoQ10 treatment may be a promising approach to reduce Tac-induced nephrotoxicity.-Yu, J. H., Lim, S. W., Luo, K., Cui, S., Quan, Y., Shin, Y. J., Lee, K. E., Kim, H. L., Ko, E. J., Chung, B. H., Kim, J. H., Chung, S. J., Yang, C. W. Coenzyme Q10 alleviates tacrolimus-induced mitochondrial dysfunction in kidney.

Ginseng increases Klotho expression by FoxO3-mediated manganese superoxide dismutase in a mouse model of tacrolimus-induced renal injury.

The antioxidant function of Klotho is well-documented as a regulatory factor implicated in countering the aging process. This study investigated whether ginseng upregulates Klotho and its antiaging signaling in a setting of calcineurin inhibitor-induced oxidative stress. Although tacrolimus treatment reduced Klotho level in the serum and kidney, ginseng treatment was found to reverse the levels. Tacrolimus-induced oxidative stress was reduced by ginseng treatment, with functional and histological improvements. Effect of ginseng on Klotho-induced manganese superoxide dismutase signaling pathway during tacrolimus treatment in mice revealed that ginseng suppressed phosphatidylinositol 3-kinase/serine-threonine kinase Akt-mediated phosphorylation of forkhead box protein O3a and promoted the binding of forkhead box protein O3a to manganese superoxide dismutase promoter. In the mitochondria, ginseng reduced mitochondrial reactive oxygen species production, mitochondrial membrane potential, and oxygen consumption rate, whereas blocking phosphatidylinositol 3-kinase activity with LY294002 enhanced them. These findings together suggested that ginseng attenuated tacrolimus-induced oxidative stress via signaling between Klotho and the phosphatidylinositol 3-kinase/serine-threonine kinase Akt/forkhead box protein O3a-related antioxidant pathway.

Therapeutic potential of coenzyme Q10 in mitochondrial dysfunction during tacrolimus-induced beta cell injury.

We previously reported that oxidative stress induced by long-term tacrolimus treatment impairs mitochondrial function in pancreatic beta cells. In this study, we aimed to investigate the therapeutic potential of coenzyme Q10, which is known to be a powerful antioxidant, in mitochondrial dysfunction in tacrolimus-induced diabetic rats. In a rat model of tacrolimus-induced diabetes mellitus, coenzyme Q10 treatment improved pancreatic beta cell function. The administration of coenzyme Q10 improved insulin immunoreactivity within islets, which was accompanied by reductions in oxidative stress and apoptosis. Assessment of the mitochondrial ultrastructure by electron microscopy revealed that coenzyme Q10 treatment increased the size, number, and volume of mitochondria, as well as the number of insulin granules compared with that induced by tacrolimus treatment alone. An in vitro study using a pancreatic beta cell line showed that tacrolimus treatment increased apoptosis and the production of mitochondrial reactive oxygen species, while cotreatment with coenzyme Q10 effectively attenuated these alterations. At the subcellular level, tacrolimus-induced impairment of mitochondrial respiration was significantly improved by coenzyme Q10, as evidenced by the increased mitochondrial oxygen consumption and ATP production. Our data indicate that coenzyme Q10 plays an important role in reducing tacrolimus-induced oxidative stress and protects the mitochondria in pancreatic beta cells. These findings suggest that supplementation with coenzyme Q10 has beneficial effects in tacrolimus-induced diabetes mellitus.

Effects of Selenium on Mercury Bioaccumulation in a Terrestrial food Chain from an Abandoned Mercury Mining Region.

Few reports of the relationship exist between mercury (Hg) and selenium (Se) from locations of severe Hg contamination in terrestrial environments. Here, we report the concentrations of Hg and Se as well as Se:Hg molar ratios in biotic samples collected from a region with a long history of Hg mining. Nitrogen isotopes (δ15N) were analyzed to confirm the trophic levels. Results showed that bird feathers at the top trophic level exhibited the highest Hg concentrations, while the lowest concentrations were found in herbivorous insects, demonstrating a significant biomagnification across the food chain. In contrast, herbivorous insects of different types (generalists vs. specialized rice pests) exhibited both the highest and the lowest concentrations of Se, indicating a lack of biomagnification. Indeed, Se was correlated positively with Hg when Se:Hg ratios were greater than one, suggesting Se:Hg molar ratios can be a controlling influence on Hg in terrestrial organisms.

Shen-Kang protects against tacrolimus-induced renal injury.

BACKGROUND/AIMS: Evidence suggests that Shen-Kang (SK), a traditional Chinese herbal medicine, protects against various types of renal injury. In this study, we evaluated whether SK treatment confers renoprotection in a rat model of chronic tacrolimus (TAC) nephropathy. METHODS: Rats were treated daily with TAC (1.5mg/kg, subcutaneously) and SK (450 mg/kg, intravenously) for 4 weeks. The effects of SK on TAC-induced renal injury were assessed by measuring renal function, urine albumin excretion, histopathology, inflammatory cell infiltration, expression of profibrotic (transforming growth factor ß1 [TGF-ß1] and TGF-ß inducible gene-h3 [ßig-h3]) and proinflammatory cytokines, oxidative stress, and apoptotic cell death. RESULTS: Administration of SK preserved glomerular integrity (fractional mesangial area and Wilms tumor 1-positive glomeruli), attenuated tubulointerstitial fibrosis, and reduced the number of ectodermal dysplasia 1-positive cells, and this was paralleled by improved urine albumin excretion and renal dysfunction. At the molecular level, SK treatment suppressed expression of TGF-ß1/Smad2/3, ßig-h3, and proinflammatory cytokines. Oxidative stress and apoptotic cell death were significantly decreased with SK treatment, and apoptosis-related genes were regulated toward cell survival (active caspase-3 and the B-cell lymphoma-2/Bcl2-associated X [Bcl-2/Bax] ratio). CONCLUSION: SK protects against TAC-induced renal injury.

Ginseng extract reduces tacrolimus-induced oxidative stress by modulating autophagy in pancreatic beta cells.

We previously reported that long-term treatment with a calcineurin inhibitor impairs autophagy process in pancreatic beta cells. This study investigated the effect of Korean red ginseng extract (KRGE) on autophagy modulated by oxidative stress. In mice with tacrolimus (Tac)-induced diabetes mellitus, KRGE alleviated islet dysfunction and decreased oxidative stress and autophagic vacuoles. In vitro, KRGE decreased autophagosome formation and attenuated lysosomal degradation, accompanied by improved beta cell viability and insulin secretion. Addition of 3-methyladenine (3-MA), an inhibitor of autophagosomes, to KRGE further improved cell viability and insulin secretion, and bafilomycin A (BA), an inhibitor of lysosomal function, reduced the effects of KRGE. At the subcellular level, Tac caused mitochondrial dysfunction (impaired mitochondrial oxygen consumption, ATP production, and increased reactive oxygen species production). But KRGE improved these parameters. The effect of KRGE on mitochondrial function enhanced by 3-MA but decreased by BA, suggesting a causal relationship between KRGE effect and autophagy modulation in Tac-induced mitochondrial dysfunction. These findings indicate that KRGE modulates autophagy favorably by reducing Tac-induced oxidative stress, and this effect is closely associated with improvement of mitochondrial function.

The protective effects of selenium on cadmium-induced oxidative stress and apoptosis via mitochondria pathway in mice kidney.

Selenium, an essential trace element, showed the significant protective effects against kidney damage induced by some heavy metals. Our previous research have found that the protection effects of selenium on ROS mediated-apoptosis by mitochondria dysfunction in cadmium (Cd)-induced LLC-PK1 cells. The present study as a continuation of our earlier one to investigate the protective effects and mechanism of selenium on Cd-induced apoptosis of kidney in vivo. Cadmium exposure increased the production of reactive oxygen species (ROS) and altered the levels of oxidative stress related biomarkers in kidney tissue. A concomitant by the loss of mitochondrial membrane potential, cytochrome c release and regulation of VDAC, Bcl-2 and Bax were observed. Apoptotic nature of cell death is confirmed by activation of caspase-3, which is also supported by histological examination. During the process, selenium played a beneficial role against Cd-induced renal damage. Pretreatment with selenium partially blocked Cd-induced ROS generation, inhibited Cd induced mitochondrial membrane potential collapse, prevented cytochrome c release, inhibited caspase activation and changed the level of VDAC, Bcl-2 and Bax. Combining all, results suggest that selenium has an ability to inhibit mitochondrial apoptotic pathway in oxidative stress mediated kidney dysfunction caused by cadmium.

The protection of selenium on cadmium-induced inhibition of spermatogenesis via activating testosterone synthesis in mice.

Selenium (Se) is an essential trance element in testis. However, the potential protective effects of Se against cadmium (Cd)-induced reproductive toxicity remained to be elucidated. Male ICR mice were orally administered by gavage with Na2SeO3 (0.1, 0.2, 0.4 mg/kg BW) for 1h prior to CdCl2 (5 mg/kg BW) alone or in combination for 15, 25 or 35 days. Cd exposure caused a significant decrease in body weight, sperm concentration and motility as well as plasma testosterone level which was accompanied by decreased antioxidant enzymatic activity of SOD and GSH-Px and by increased lipid peroxidation (as malondialdehyde, MDA). Se pretreatment compensated deficits in the sperm parameters (concentration, motility and morphology) induced by Cd. Se (0.4 mg/kg BW) treatment significantly increased serum testosterone level that was reduced by Cd (on 15th, 25th and 35th day) (P<0.01). Se treatment ameliorated Cd-induced reduction in testicular steroidogenic acute regulatory (StAR) and 17ß-hydroxysteroid dehydrogenase (17ß-HSD) activities. The present study suggest that the protective potential of Se against Cd-induced reprotoxicity might be due to up-regulation StAR and testosterone synthetic enzyme activity, which could be useful for increasing testosterone synthesis for achieving optimum protection in sperm quality and spermatogenesis.

Liquiritigenin inhibits serum-induced HIF-1α and VEGF expression via the AKT/mTOR-p70S6K signalling pathway in HeLa cells.

Liquiritigenin (LQ) is a non-toxic dietary flavonoid with chemopreventive and anticancer properties. However, the mechanism of its antiangiogenesis remains unclear. Hypoxia-inducible factor-1α (HIF-1α) and its downstream target, vascular endothelial growth factor (VEGF), play a critical role in tumour angiogenesis and represent an attractive chemotherapeutic target. In this study, we investigated the effect of LQ on the molecular mechanism of angiogenesis. We found that LQ inhibited VEGF expression at both mRNA and protein levels. Liquiritigenin did not affect HIF-1α expression at the mRNA level, but it dramatically inhibited both serum- and mimicked hypoxic-induced HIF-1α protein accumulation in HeLa cells. Furthermore, we showed that LQ inhibited serum-induced expression of HIF-1α by reducing its stability and decreased the synthesis in a dose-dependent manner. Mechanistically, we demonstrated that LQ inhibited HIF-1α and VEGF expression involved in blocking the protein kinase B (PKB/Akt) signalling pathway, and the mechanisms correlated with dephosphorylation of the mammalian target of rapamycin (mTOR) and its effector ribosomal protein S6 kinase (p70S6K). In addition, LQ inhibited VEGF-induced formation of capillary-like structures in human umbilical vein endothelial cells (HUVEC). Taken together, our study provided valuable insights into the mechanism of antiangiogenic effect of LQ.

[Analysis of three lamivudine-resistant HBV mutants with the method of restriction enzyme digestion and its application].

OBJECTIVE: To investigate the prevalence of three lamivudine-resistant HBV mutants in lamivudine-treated Chinese patients. METHODS: Using three pairs of of HBV polymerase gene B and C domain fragments were amplified by PCR. The PCR products were then digested by restriction enzyme Nde I and Nla III. The digested products were analyzed by electrophoresis. With this method, the prevalence of the three lamivudine-resistant mutants in lamivudine-treated Chinese patients was investigated. RESULTS: After Nde I digestion of p24 and p29 amplified product, HBV wild type could be easily separated from YMDD mutant. At the same time, YIDD could be separated from YVDD mutant after Nla III digestion of p24 and p29 amplified product. By this method, the authors found that these eleven patients were infected with lamivudine-resistant mutants. Six of them were infected with M5501 mutant; five were infected with M550V mutant (one of them had both M550V and L526M mutations). CONCLUSION: The method of the present study was demonstrated to be an easy way to detect HBV lamivudine-resistant mutants and can be applied to clinical monitoring of lamivudine resistance.