Effect of levocarnitine/iron saccharate combination on renal anaemia and oxidative stress in patients undergoing haemodialysis

Purpose: To investigate the effect of a combination of levocarnitine and iron saccharate on the treatment of renal anaemia and oxidative stress in patients undergoing haemodialysis.Methods: A total of 156 patients with renal anaemia were divided randomly into control (78 cases) and test groups (78 cases). Patients in the control group were treated with erythropoietin (EPO), iron saccharate, and conventional symptomatic treatment, while patients in the test group were treated with levocarnitine additionally. Anaemia indices, oxidative stress indices, response rate, and EPO dose were compared.Results: At week 28, the levels of hemoglobin b (Hb), hematocrit (Hct), serum ferritin (SF), and transferrin saturation (TSAT) in the test group were 92.72 ± 12.51 g/L, 34.74 ± 5.89 vol %, 245.61 ± 81.35 ng/mL, and 24.34 ± 5.32 %, respectively, which were much lower than the levels in the test group (114.36 ± 12.27 g/L, 40.23 ± 5.78 vol %, 345.07 ± 85.93 ng/mL, and 29.76 ± 5.41 %, respectively; p < 0.05). The levels of advanced oxidation protein products (AOPP) and malonaldehyde (MDA) in the test group were much higher than those of the control group (121.77 ± 31.65 nmol/L vs 89.65 ± 30.53 nmol/L; 9.58 ± 2.64 nmol/L vs 4.81 ± 2.57 nmol/L, respectively (p < 0.05). EPO was maintained at a high dose from the beginning of treatment to week 28 in the control group, whereas in the test group, EPO dose was reduced gradually. The response rate in the test group was higher than that in the control group (92.30 % vs 76.90 %; p < 0.05).Conclusion: Levocarnitine/iron saccharate combination had a significant positive effect on the treatment of renal anaemia. It effectively relieved oxidative stress reactions and reduced the dose of EPO required.Keywords: Haemodialysis, Renal anaemia, Oxidative stress reaction, Levocarnitine, Iron saccharate, Erythropoieti

Chloroquine prevents acute kidney injury induced by lipopolysaccharide in rats via inhibition of inflammatory factors

Purpose: To investigate the role of chloroquine (CQ) in lipopolysaccharide (LPS)-induced renal injury in rats.Methods: Rats were assigned to one of four groups (n = 10). Control group was only given saline solution, whereas the model control, LPS + CQ, and LPS + yohimbine (YOH) + CQ groups were administered LPS intraperitoneally. At the end of the study, blood urea nitrogen (BUN) and creatinine (Cr) levels were determined.Results: CQ treatment significantly decreased the blood concentrations of tissue necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-18, BUN, and Cr in the model control rats. There were also significant decreases in the levels of high mobility group protein 1 and kidney injury molecule-1 in the renal injury rats compared to the model control group. However, the inhibitory effects of CQ in the LPS-treated rats were blocked by treatment with YOH, an α-2-adrenergic receptor antagonist.Conclusions: Treatment with CQ attenuates LPS-induced renal injury by inhibiting inflammatory response.Keywords: Creatinine, Chloroquine, Inflammatory reactions, Kidney injury, Lipopolysaccharid

A parthenogenetic maternal and double paternal contribution to an ovotesticular disorder of sex development

BACKGROUND: An ovotesticular disorder of sex development (OT-DSD) was rarely found in human. The mechanism causing such condition is poorly understood. We hereby reported a 11-year-old child with OT-DSD and a karyotype 46,XX/46,XY, a single maternal and double paternal genetic contribution to the patient. RESULTS: Fluorescence in situ hybridization (FISH), blood grouping, HLA (human leukocyte antigen) haplotyping and a genome-wide scanning of lymphocytes with 398 short tandem repeat microsatellite markers were performed to investigate the origin of the cell lines concerned. ABO typing revealed that two populations of red cells were in the patient, which were group A and group B, both from paternal alleles. HLA haplotyping showed the patient had three haplotypes. Haplotype 1 was inherited from maternity, haplotype 2 and 3 were from paternity. The STR microsatellite analysis showed 25 of the 74 fully informative markers in both parents, three alleles were inherited: one of them was from mother, another two were from father. Seventeen of the thirty-eight paternal markers, the patient inherited two paternal alleles. For 121 informative maternal markers, the patient had a single maternal allele. There were two distinct alleles in locus DXS6810 and DXS1073 on X-chromosome, in which one was from the mother and the other from the father. CONCLUSIONS: The patient was a single maternal and double paternal genetic, which was a type of a parthenogenetic division of a maternal haploid nucleus into two identical nuclei, followed by fertilization by two spermatozoa and fusion of the two zygotes into a single individual at the early embryonic stage. To the best of our knowledge, this is the oldest OT-DSD case of parthenogenetic chimerism. These data provide additional evidence that a parthenogenetic maternal and double paternal contribution causes 46,XX/46,XY OT-DSD

Comparing the contents, functions and neonicotinoid take-up between floral and extrafloral nectar within a single species (Hemerocallis citrina Baroni)

BACKGROUND AND AIMS: Many angiosperms can secrete both floral (FN) and extrafloral (EFN) nectar. However, much remains unclear about how EFN and FN differ in secretion, composition and ecological function, especially when both FN and EFN are secreted on flowers of the same species. METHODS: Hemerocallis citrina flowers secrete both FN and EFN. The FN and EFN traits including volume, presentation pattern and temporal rhythms of secretion were compared by field observation. Sugar and amino acid contents were analysed using regular biochemical methods, whereas the proteome was investigated by combined gel-based and gel-free approaches. Animal feeders on FN and EFN were investigated by field observation. Hemerocallis citrina plants were exposed by soil drenching to two systemic insecticides, acetamiprid and imidacloprid, and the concentration of these in FN and EFN was measured by ultra-high performance liquid chromatography coupled with mass spectrometry. KEY RESULTS: Hemerocallis citrina FN was concentrated and sucrose dominant, secreted in the mature flower tube and served as a reward for pollinators. Conversely, EFN was hexose rich, more dilute and less rich in sugar and amino acids. EFN was secreted on the outside of developing floral buds, and was likely to attract predatory animals for defence. EFN had fewer phenolics, but more pathogenesis-related components, such as chitinase and glucanase. A significantly different proteomic profile and enzymatic activities between FN and EFN suggest that they had different biosynthesis mechanisms. Both neonicotinoid insecticides examined became present in both nectar types soon after application, but in greater concentration within EFN; EFN also attracted a wider range of insect species than FN. CONCLUSIONS: Hemerocallis citrina FN and EFN differed in production, composition and ecological function. The EFN pathway could be a significant way for neonicotinoids to enter the wild food chain, and must be considered when evaluating the risks to the environment of other systemic insecticides

Bluetongue virus capsid protein VP5 perforates membranes at low endosomal pH during viral entry.

Bluetongue virus (BTV) is a non-enveloped virus and causes substantial morbidity and mortality in ruminants such as sheep. Fashioning a receptor-binding protein (VP2) and a membrane penetration protein (VP5) on the surface, BTV releases its genome-containing core (VP3 and VP7) into the host cell cytosol after perforation of the endosomal membrane. Unlike enveloped ones, the entry mechanisms of non-enveloped viruses into host cells remain poorly understood. Here we applied single-particle cryo-electron microscopy, cryo-electron tomography and structure-guided functional assays to characterize intermediate states of BTV cell entry in endosomes. Four structures of BTV at the resolution range of 3.4-3.9 Å show the different stages of structural rearrangement of capsid proteins on exposure to low pH, including conformational changes of VP5, stepwise detachment of VP2 and a small shift of VP7. In detail, sensing of the low-pH condition by the VP5 anchor domain triggers three major VP5 actions: projecting the hidden dagger domain, converting a surface loop to a protonated β-hairpin that anchors VP5 to the core and stepwise refolding of the unfurling domains into a six-helix stalk. Cryo-electron tomography structures of BTV interacting with liposomes show a length decrease of the VP5 stalk from 19.5 to 15.5 nm after its insertion into the membrane. Our structures, functional assays and structure-guided mutagenesis experiments combined indicate that this stalk, along with dagger domain and the WHXL motif, creates a single pore through the endosomal membrane that enables the viral core to enter the cytosol. Our study unveils the detailed mechanisms of BTV membrane penetration and showcases general methods to study cell entry of other non-enveloped viruses