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Long-term hypertension can lead to hypertensive heart disease, which ultimately progresses to heart failure. As an angiotensin receptor blocker antihypertensive drug, allisartan can control blood pressure, and improve cardiac remodeling and cardiac dysfunction caused by hypertension. The aim of the present study was to investigate the protective effects of allisartan on the heart of spontaneously hypertensive rats (SHRs) and the underlying mechanisms. SHRs were used as an animal model of hypertensive heart disease and were treated with allisartan orally at a dose of 25 mg/kg/day. The blood pressure levels of the rats were continuously monitored, their body and heart weights were measured, and their cardiac structure and function were evaluated using echocardiography. Wheat germ agglutinin staining and Masson trichrome staining were employed to assess the morphology of the myocardial tissue. In addition, transcriptome and proteome analyses were performed using the Solexa/Illumina sequencing platform and tandem mass tag technology, respectively. Immunofluorescence co-localization was conducted to analyze Nrf2 nuclear translocation, and TUNEL was performed to detect the levels of cell apoptosis. The protein expression levels of pro-collagen I, collagen III, phosphorylated (p)-AKT, AKT, p-PI3K and PI3K, and the mRNA expression levels of Col1a1 and Col3a1 were determined by western blotting and reverse transcription-quantitative PCR, respectively. Allisartan lowered blood pressure, attenuated cardiac remodeling and improved cardiac function in SHRs. In addition, allisartan alleviated cardiomyocyte hypertrophy and cardiac fibrosis. Allisartan also significantly affected the 'pentose phosphate pathway', 'fatty acid elongation', 'valine, leucine and isoleucine degradation', 'glutathione metabolism', and 'amino sugar and nucleotide sugar metabolism' pathways in the hearts of SHRs, and upregulated the expression levels of GSTM2. Furthermore, allisartan activated the PI3K-AKT-Nrf2 signaling pathway and inhibited cardiomyocyte apoptosis. In conclusion, the present study demonstrated that allisartan can effectively control blood pressure in SHRs, and improves cardiac remodeling and cardiac dysfunction. Allisartan may also upregulate the expression levels of GSTM2 in the hearts of SHRs and significantly affect glutathione metabolism, as determined by transcriptome and proteome analyses. The cardioprotective effect of allisartan may be mediated through activation of the PI3K-AKT-Nrf2 signaling pathway, upregulation of GSTM2 expression and reduction of cardiomyocyte apoptosis in SHRs. [ABSTRACT FROM AUTHOR]

Background: The plasmid-encoded multidrug efflux pump oqxAB confers bacterial resistance primarily to olaquindox, quinolones, and chloramphenicol. The aims of this study were to investigate the prevalence of oqxAB among Escherichia coli isolates from dogs, cats, and humans in Henan, China and the susceptibilities of E. coli isolates to common antibiotics. Methods: From 2012 to 2014, a total of 600 samples which included 400 rectal samples and 200 clinical human specimens were tested for the presence of E. coli. All isolates were screened for oqxAB genes by PCR and sequencing. The MICs of 11 antimicrobial agents were determined by the broth microdilution method. A total of 30 representative oqxAB-positive isolates were subjected to ERIC-PCR and MLST. Additionally, conjugation experiments and southern hybridizations were performed. Results: Of 270 isolates, 58.5% (62/106) of the isolates from dogs, 56.25% (36/64) of the isolates from cats, and 42.0% (42/100) of the isolates from humans were positive for the oqxAB. Olaquindox resistance was found for 85.7%-100% of oqxAB-positive isolates. Of oqxAB-positive isolates from dogs, cats, and humans, ciprofloxacin resistance was inspected for 85.8%, 59.1%, and 93.8%, respectively. Several oqxAB-positive isolates were demonstrated by ERIC-PCR and MLST, and have high similarity. Phylogenetic analysis showed that oqxAB-positive isolates could be divided into 7 major clusters. OqxAB-positive conjugants were obtained, southern hybridization verified that the oqxAB gene complex was primarily located on plasmids. Conclusion: In conclusion, oqxAB-positive isolates were widespread in animals and humans in Henan, China. Carriage of oqxAB on plasmids of E. coli isolates may facilitate the emergence of multidrug resistant and its transmission via horizontal transfer, and might pose a potential threat to public health. [ABSTRACT FROM AUTHOR]

Integrative conjugative elements (ICEs) are important carriers for disseminating resistance genes. We have previously reported a novel element ICE Hpa1 carrying seven antibiotic resistance genes, which could be self-transmissible relying on the novel T4SS. To identify novel ICE Hpa1 variants from 211 strains and novel T4SS encoded in ICE Hpa1 , and to explore the relationships in these ICEs, four complete sequences of ICEs were identified by WGS analysis and antimicrobial susceptibility testing was determined by broth microdilution. In addition, a comparative analysis of these ICEs was conducted with bioinformatic tools, and the transfer abilities of these ICEs were confirmed by conjugation. Four ICE Hpa1 variants ICE Gpa1818 , ICE Gpa1808 , ICE Gpa1807 , and ICE Gpa1815 with different resistance gene profiles were characterized, and their hosts showed different resistance spectrums. All ICEs shared the same backbone and were inserted into the tRNA Leu site, and all resistance regions were inserted into the same target site between the accessory and integration regions. This study analyzed complete sequences of ICEs from the ICE Hpa1 family and identified novel T4SS and insertion element IS Gpa2 . Diverse resistance genes extensively exist in these ICEs, serving as a reservoir for resistance genes and facilitating their dissemination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sun, Zhang, Miao, Zhai, Pan, Yuan, Yan, Wu and Hu.)

Introduction. The bla CTX-M-3 gene has rarely been reported in Morganella morganii strains and its genetic environment has not yet been investigated. Aim. To identify the bla CTX-M-3 gene in M. morganii isolated from swine and characterize its genetic environment. Methodology. A M. morganii isolate (named MM1L5) from a deceased swine was identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and subjected to antimicrobial susceptibility testing. The bla genes were detected and then the genetic location and environment of bla CTX-M-3 were investigated by Southern blot and PCR mapping, respectively. The M. morganii bla CTX-M-3 gene was cloned and expressed in Escherichia coli . Results. Isolate MM1L5 harboured the bla CTX-M-3 and bla TEM-1 genes. The bla CTX-M-3 gene, located on the chromosome, was co-carried with an IS 26 and bla TEM-1 gene by a novel 6361 bp IS 26 -flanked composite transposon, designated Tn 6741 . This transposon consisted of a novel bla CTX-M-3 -containing module, IS 26 -ΔIS Ecp1-bla CTX-M-3 -Δ orf477 -IS 26 (named Tn 6710 ), and a bla TEM-1 -containing module, IS 26 -Δ orf477-bla TEM-1 -tnpR-IS 26 , differing from previous reports. Phylogenetic analysis showed a significant variation based on the sequence of Tn 6741 , as compared to those of other related transposons. Interestingly, although the cloned bla CTX-M-3 gene could confer resistance to ceftiofur, cefquinome, ceftriaxone and cefotaxime, one amino acid substitution (Ile-142-Thr) resulted in a significant reduction of resistance to these antimicrobials. Conclusion. This is the first time that bla CTX-M-3 has been identified on a chromosome from a M. morganii isolate. Furthermore, the bla CTX-M-3 gene was located with an IS 26 element and bla TEM-1 gene on a novel IS 26 -flanked composite transposon, Tn 6741 , suggesting that Tn 6741 might act as a reservoir for the bla CTX-M-3 and bla TEM-1 genes and may become an important vehicle for their dissemination among M. morganii .