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Abstract Background Porcine circovirus type 2 (PCV2) is associated with post-weaning multi-systemic wasting syndrome (PMWS) in young weaned pigs. Immune stimulation was found to activate the replication of PCV2 and exacerbate the clinical outcome of the infection. Proper amount of interferon-α (IFN-α) is able to enhance PCV2 infection and production in Porcine kidney-15 (PK-15) cells when administered after inoculation. Methods In the present study, luciferase reporter assays, construction of mutant viruses, Analysis the replication efficiency and the response to IFN-α treatment in PK-15 cells and animal experiments were carried out to analyze the function of interferon-stimulated response element (ISRE) of PCV2 and its role during viral replication in vitro and in vivo. Results A functional viral ISRE sequence, 5′-CTGAAAACGAAAGA-3′, was identified in Rep gene promoter (Prep) of PCV2. PCV2 Prep is composed of two mini promoters, the proximal one span the sequence +1 to -106, containing an ISRE while the distal mini promoter is composed of three tandem GC box like sites locate at -85 to -194. It was demonstrated that viral ISRE is necessary for porcine IFN-α initiated luciferase expression enhancement and it plays an important role in affecting the replication efficiency of PCV2 in vivo and in vitro. Conclusions These findings provide a theoretical basis for the Phenomenon of immunostimulation is able to enhance PCV2 infection, and improve the understanding of the complicated mechanisms involved in the host and pathogen interactions of PCV2.

Salt‐induced hypertension is one of the major issues worldwide and one of the main factors involved in heart and kidney failure. The objective of this study was to investigate the potential role of Benincasa hispida extracts on high salt‐induced hypertension in Dahl‐salt sensitive (D‐SS) rats and to find out the metabolic and biochemical pattern involved in the reduction of hypertension. Twenty‐six Dahl salt‐sensitive (D‐SS) rats were selected and divided into four groups. The metabolic strategy was applied to test the extracts on salt‐sensitive hypertension in kidney. Gas Chromatography–Mass spectrometry (GC–MS) was used to identify the potent biochemical profile in renal medulla and cortex of rat kidneys. The differential metabolites of cortex and medulla, enrichment analysis and pathway analysis were performed using metabolomics data. The GC–MS data revealed that 24 different antihypertensive metabolites was detected in renal cortex, while 16 were detected in renal medulla between different groups. The significantly metabolic pathways namely citrate cycle, glutathione metabolism, glycine, serine, and threonine metabolism, glyoxylate and dicarboxylate metabolism, glycerolipid metabolism, alanine, aspartate and glutamate metabolism in renal cortex and glycerolipid metabolism, pentose phosphate pathway, citrate cycle, glycolysis, glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis in renal medulla were involved in the process of Hypertension. The results suggest that the extract mainly alter the metabolic pathways of amino acid in Dahl salt‐sensitive rats and its antioxidant potential reduced the hypertension patterns of Salt‐sensitive rat. The antihypertensive components malic acid, aspartic acid, and glycine of extract can be used as therapeutic drugs to protect kidneys from salt‐induced hypertension. Practical applications: Hypertension is a multifactorial disease and one of the risk factors for heart and kidney failure. Benincasa hispida is a widely used vegetable in China, which belongs to the Cucurbitaceae family. Benincasa hispida (wax gourd) has been used in traditional Chinese medicine for the treatment of inflammation and hypertension. The Benincasa hispida contains many compounds such as amino acids, carbohydrates, volatile compounds, vitamins, and minerals. The amino acid present in the pulp of Benincasa hispida are ornithine, threonine, aspartate, glutamate, serine, glycine, proline, alanine, valine, cysteine, isoleucine, tyrosine, leucine, lysine, phenylalanine, histidine, arginine, and γ‐aminobutyric acid. Our results showed that Benincasa hispida is one of the potent natural antioxidants and can maintain normal blood pressure in Dahl salt‐sensitive rats (D‐SS). In conclusion, the current results provide good theoretical basis for the development and research using Benincasa hispida as an effective natural antioxidant for hypertension. [ABSTRACT FROM AUTHOR]

High salt diet (HSD, 8% NaCl) contributes to salt-sensitive hypertension, this study aimed to determine the effect of HSD on salt-sensitive hypertension by combining proteomic with metabolomics methods. Salt-sensitive rats were fed on HSD and normal salt diet (NSD, 0.4% NaCl) for two weeks before further analysis. Proteomic analysis showed the differential expression proteins (DEPs) were primarily mapped in the tricarboxylic acid (TCA)-cycle, glycolysis/gluconeogenesis, and other pathways associated with multiple amino acids. HSD decreased the medullary activities and protein expression level of two key enzymes of TCA-cycle, MDH and NADP+-IDH. Metabolomics showed three serous TCA-cycle-associated compounds, including decreased malic acid, decreased citric acid, and increased fumaric acid were differentially detected, which resulted in a decrease in NO content and an increase in H 2 O 2 content in serum. The content of GSH, GSH/GSSG ratio, and synthesis substrates of GSH-cysteine and glycine, were significantly decreased by HSD, thus attenuated the antioxidant system in the renal medulla. HSD enhanced the medullary pentose phosphate pathway, which finally increased the concentration of NADPH and NADP+, NADPH/NADP+, and the activity of NADPH oxidase in the renal medulla. Additionally, HSD enhanced the glycolysis pathway in the renal medulla. In summary, HSD significantly weakened the TCA cycle, and attenuated the antioxidant system in the renal medulla, which finally contributed to salt-sensitive hypertension. Image 1 • High salt diet weakened the medullary TCA cycle, decreased malic acid and citric acid, increased fumaric acid in serum. • High salt diet decreased the synthesis substrates of medullary GSH, thus attenuated the antioxidant system. • High salt diet enhanced medullary pentose phosphate pathway, increased NADPH/NADP+ and the activity of NADPH oxidase. [ABSTRACT FROM AUTHOR]

Salt-sensitive hypertension is a risk factor for cardiovascular disease. Previous studies have shown that insufficient arginine in the kidney caused by metabolic imbalance is an important factor in salt-sensitive hypertension. Whether the high nitrogen content of histidine can affect the balance of nitrogen metabolism in Dahl salt-sensitive (SS) rats. This article aimed to study the effects of oral histidine on salt-sensitive hypertension, kidney damage and metabolic patterns of high-salt diet in SS rats. Adult rats were divided into four groups, and blood pressure was measured using a non-invasive tail-cuff system. Gas chromatography-mass spectrometry analyzed metabolites in serum and kidney tissues. High-salt diet significantly increased the blood pressure of rats and aggravated kidney damage. Of note, histidine can attenuate salt-sensitive hypertension and kidney damage by improving metabolic pattern, reducing Reactive Oxygen Species (ROS) and increasing nitric oxide levels in SS rats. These results suggest that histidine could be a potential adjuvant to prevent and control salt-sensitive hypertension. Unlabelled Image • Salt sensitive rats developed salt-sensitive hypertension and renal injury under high salt. • Histidine significantly decreased ROS, increased nitric oxide level and altered the metabolic profile of SS rats. • Some amino acids metabolic pathways suggested a vital role in the antihypertension. • Histidine has prophylaxis function on salt-sensitive hypertension. [ABSTRACT FROM AUTHOR]