Application progress of ischemic preconditioning in ischemia-reperfusion injury of renal allografts / 器官移植

Kidney transplantation is more efficacious compared with other organ transplantations. Nevertheless, postoperative complications, such as renal ischemia-reperfusion injury (IRI), severely affect the survival rate and quality of life of recipients. How to mitigate the IRI of renal allografts has become one of the key topics in the field of kidney transplantation. At present, ischemic preconditioning enables renal allografts to adapt to ischemia, which is one of the effective methods to prevent the progression of IRI. However, the underlying mechanism remains elusive. In this article, the application of ischemic preconditioning in IRI, the regulation mechanism of ischemic preconditioning on the IRI of renal allografts at the cellular level and intracellular signaling pathway, and clinical application value and prospect of ischemic preconditioning were reviewed, aiming to provide reference for alleviating the IRI of renal allografts, enhancing the survival rate of the recipients and renal allografts and improving the quality of life of recipients.

Active vitamin D3 plays a protective role in podocytes of diabetic rats by regulating autophagy activity / 中华内分泌代谢杂志

Objective To investigate the protective effect and mechanism of active vitamin D3 on podocyte injury in type 1 diabetic rats.Methods Animals were randomly divided into normal control group (NC group),diabetic nephropathy group (DN group),diabetes nephropathy plus active vitamin D3 group (DN + VD group).Random tail vein blood glucose was measured and 24 hours of urine was collected every 3 weeks to observe the dynamic changes of blood glucose and 24-hour urine volume and urinary albumin.Rats were sacrificed at the end of 18th week,the kidney weight to body weight ratio,serum creatinine,blood urea nitrogen,serum calcium,and serum phosphorus levels were measured.Pathological in glomeruli were observed by PAS staining.Immunohistochemistry and Western blotting were used to observe the expression of slit diaphragms proteins including Nephrin,Podocin,and vitamin D receptor protein VDR.The mRNA level of autophagy-related protein P62 was detected by realtime quantitative PCR,and expression of autophagy-related protein including LC3B/A,Beclin1,and P62 were detected by Western blotting.Ultrastructure of podocytes and autopbagosomes in podocytes were observed by electron microscopy.Results Levels of serum creatinine,blood urea nitrogen,and blood glucose in diabetic rats were higher than those in NC group (P＜0.05),but without significant difference between DN and DN+VD groups (P＞0.05).Compared with the DN group,the urinary protein and kidney weight to body weight ratio in the DN +VD group were significantly lower (P＜ 0.05).Mesangial matrix hyperplasia and basement membrane thickening were improved,and podocyte fusion and shedding were partially reversed.The expressions of Nephrin,Podocin,VDR,LC3B/A and Beclin1 were increased,and P62 mRNA and protein were down-regulated (P ＜ 0.05).The number of autophagosomes in podocytes increased.Besides,positive correlations were found between Nephrin and Beclin 1 (r =0.939 8,P＜0.05),as well as Nephrin and VDR (r=0.948 3,P＜0.05),and Beclin1 andVDR (r=0.9093,P＜0.05).Conclusion Active vitamin D3 inhibits the injury of diabetic nephropathy podocytes by up-regulating VDR expression and enhancing autophagy activity,thereby reducing proteinuria and delaying the development of diabetic nephropathy.

Metabonomics delineates allergic reactions induced by Shuang-huang-lian injection in rats using ultra performance liquid chromatography-mass spectrometry / 中国天然药物

Shuang-huang-lian Injection (SHLI) is the first successfully developed drug from traditional Chinese medicine (TCM) powder for injection, since its use for the treatment of acute respiratory tract infection, pneumonia, influenza, etc. At the same time, its allergic reactions have also emerged, which limits clinical applications. However, few scholars pay attention to the mechanism of allergic reactions. In this present study, metabonomics technology was used to explore the changes in endogenous metabolites in urine of the rat model of SHLI induced allergic reaction; we and analyzed the metabolites, metabolic pathway, and the mechanism which were closely related to the allergic reactions. The levels of serum histamine and tryptase were examined and changes in histomorphology were also observed. Based on the UPLC-Q-TOF/MS metabonomics, we carried out the pattern recognition analysis, selected potential biomarkers associated with allergic reactions, and explored the pathological mechanism for SHLI induced allergic reaction, which laid the foundation for the safety research of SHLI. Our results showed that SHLI increased the levels of serum histamine and tryptase in rats with allergic reaction; we determined 15 biomarkers in rat allergic reaction model induced by SHLI and found multiple metabolic pathways involved, such as metabolism of linolenic acid, phenylalanine, amino acid, 2-oxo acid, and purine and other metabolic pathways.

Metabonomics delineates allergic reactions induced by Shuang-huang-lian injection in rats using ultra performance liquid chromatography-mass spectrometry / 中国天然药物

Shuang-huang-lian Injection (SHLI) is the first successfully developed drug from traditional Chinese medicine (TCM) powder for injection, since its use for the treatment of acute respiratory tract infection, pneumonia, influenza, etc. At the same time, its allergic reactions have also emerged, which limits clinical applications. However, few scholars pay attention to the mechanism of allergic reactions. In this present study, metabonomics technology was used to explore the changes in endogenous metabolites in urine of the rat model of SHLI induced allergic reaction; we and analyzed the metabolites, metabolic pathway, and the mechanism which were closely related to the allergic reactions. The levels of serum histamine and tryptase were examined and changes in histomorphology were also observed. Based on the UPLC-Q-TOF/MS metabonomics, we carried out the pattern recognition analysis, selected potential biomarkers associated with allergic reactions, and explored the pathological mechanism for SHLI induced allergic reaction, which laid the foundation for the safety research of SHLI. Our results showed that SHLI increased the levels of serum histamine and tryptase in rats with allergic reaction; we determined 15 biomarkers in rat allergic reaction model induced by SHLI and found multiple metabolic pathways involved, such as metabolism of linolenic acid, phenylalanine, amino acid, 2-oxo acid, and purine and other metabolic pathways.

Study on the Mechanism of Celosia cristata N-butanol Extracts in the Improvement of Dysfunctional Uter-ine Bleeding of Rats / 中国药房

OBJECTIVE:To study the improvement effect of Celosia cristata n-butanol extracts on dysfunctional uterine bleed-ing of rats,and explore its mechanism. METHODS:60 pregnant SD rats were randomly divided into blank group,model group, Gongxuening capsule group (positive control,0.07 g/kg) and C. cristata n-butanol extracts high-dose,medium-dose,low-dose groups(4.32,2.16,1.08 g/kg),10 in each group. Except for the blank group,rats in other groups were intragastrically given mife-pristone and misoprostol on 7th of pregnancy for resulting incomplete abortion to induce models of dysfunctional uterine bleeding. Then rats in administration groups were intragastrically given relevant medicines,rats in blank group and model group were intra-gastrically given normal saline once every morning and evening,for 7 d. On 8th d of pregnancy,uterine bleeding amount,and thromboxane (TXA2),prostacyclin (PGI2) and tumor necrosis factor α(TNF-α) contents in serum were determined. RESULTS:Compared with blank group,uterine bleeding amount in model group was significantly increased(P<0.01),TXA2 content in se-rum was significantly reduced,PGI2 and TNF-α contents were significantly increased(P<0.01). Compared with model group,uter-ine bleeding amounts in administration groups were significantly reduced,TXA2 content in serum was significantly increased(P<0.01);PGI2 and TNF-α contents in serum in Gongxuening capsule group and C. cristata n-butanol extracts high-dose group and TNF-α content in serum in C. cristata n-butanol extracts medium-dose group were significantly reduced (P<0.01). CONCLU-SIONS:C. cristata n-butanol extracts show obvious improvement effect on incomplete drug abortion-induced dysfunctional uterine bleeding of rats,and the mechanism may be related to the regulation of TXA2/PGI2 dynamic balance and inhibition of TNF-α tran-sient secretion.

Screening and characterization of aptamers of Cepsilon3-Cepsilon4 protein / 药学学报

In order to obtain nucleotides aptamers bind to IgE, 80 bp nucleotides single-stranded DNA library containing 40 random nucleotides was designed and synthesized. Oligonucleotides that bind to human Cepsilon3-Cepsilon4 protein were isolated from ssDNA pools by the systematic evolution of ligands by exponential enrichment (SELEX) method using nitrocellulose filters as screening medium. Through the optimization of critical PCR and asymmetric PCR parameters including annealing temperature, cycles, and molar ratios of target protein and ssDNA etc, a suitable screening system was established. The aptamers of Cepsilon3-Cepsilon4 protein with high affinity and high specificity were identified by ELISA with biotin-streptavidin-horseradish peroxidase system, and its primary sequence and second structure were analyzed by DNAMAN package and DNA folding sever after being cloned and sequenced. Moreover, target protein was bound to one aptamer and another aptamer modified with biotion together forming a sandwich-like complex, which was captured in microwell to detect IgE concentration using the optimal combination in the sandwich method named enzyme-linked aptamers sorption assay (ELASA). The method could be used for the quantitative detection of human IgE, and whose sensitivity reached to 120 ng x mL(-1).

Progress in the study of allergic disease drugs targeting on IgE/FcepsilonRI signaling pathway / 药学学报

Allergic diseases have become global social health problems. The binding of IgE with its high affinity receptor FcepsilonRI plays a key step in I-type allergy. Recently, more and more key molecules on the IgE/FcepsilonRI signaling transduction pathway were to be the drug candidates against allergic diseases, with in-depth study of FcepsilonRI signal pathway gradually. The main drugs include molecule antibodies, peptides, vaccines, fusion proteins, small molecules, and other drugs related to IgE/FcepsilonRI. The recent progress in the study of mechanisms of representative drugs targeting on IgE/FcepsilonRI signaling pathway was reviewed in this article.