The global distribution of canine parvovirus (CPV-2) derived from a closely related carnivore parvovirus poses a considerable threat to the dog population. The virus is continuously undergoing genetic evolution, giving rise to several variants. To investigate the prevalence of Chinese CPV-2 strains in recent years, a total of 30 CPV-2 strains were collected from 2018 to 2021 and the VP2 gene was sequenced and analyzed. Two variants, new CPV-2a (297Ala, 426Asn) and CPV-2c (426Glu), were identified. In contrast to previous reports, the CPV-2c variant has gained an epidemiological advantage over the new CPV-2a variant in China. To compensate for the relatively small sample size, 683 Chinese CPV-2 strains identified between 2014 and 2019 were retrieved from the GenBank database and previous publications, and analyses of these strains further supported our findings, which should be considered since the CPV-2c variant has been frequently associated with immune failure in adult dogs. VP2 protein sequence analysis revealed several amino acid substitutions, including Ala5Gly, Pro13Ser, Phe267Tyr, Tyr324Ile, Gln370Arg, Thr440Ala, and Lys570Arg. Phylogenetic analysis of full-length VP2 gene indicated a close relationship between Chinese strains and other Asian strains, suggesting mutual transmission between Asian countries. Furthermore, intercontinental transmission is a cause for concern. Surprisingly, two feline panleukopenia virus (FPV) strains with the Ile101Thr mutation in the VP2 protein were identified in canine fecal samples; FPV has been considered incapable of infecting dogs. This study clarified the epidemic characteristics of Chinese CPV-2 strains detected between 2014 and 2019, offering a reference for epidemic control. In addition, the detection of FPV in canine samples may provide information for future studies on the evolution of carnivore parvoviruses.
Heat stress (HS) often causes sudden death of humans and animals due to heart failure, mainly resulting from the contraction of cardiac microvasculature followed by myocardial ischemia. Cardiac microvascular endothelial cells (CMVECs) play an important role in maintaining vasodilatation. Aspirin (ASA) is well known for its protective abilities of febrile animals. However, there is little knowledge about molecular resistance mechanisms of CMVECs and which role ASA may play in this context. Therefore, we used a heat stress model of rat cardiac microvascular endothelial cell cultures in vitro and investigated the cell injuries and molecular resistance mechanism of CMVECs caused by heat stress, and the effect of aspirin (ASA) on it. HS induced severe pathological damage of CMVECs and cellular oxidative stress and dysfunction of NO release. Hsp90 was proven to be indispensable for resisting HS-injury of CMVECs through PI3K-Akt and PKM2 signaling pathways. Meanwhile, PKM2 functioned in reducing Akt phosphorylation. ASA treatment of CMVECs induced a significant expression of Hsp90, which promoted both Akt and PKM2 signals, which are beneficial for relieving HS damage and maintaining the function of CMVECs. Akt activation also promoted HSF-1 that regulates the expression of Hsp70, which is known to assist Hsp90′s molecular chaperone function and when released to the extracellular liquid to protect myocardial cells from HS damage. To the best of our knowledge, this is the first study to show that HS damages CMVECs and the protection mechanism of Hsp90 on it, and that ASA provides a new potential strategy for regulating cardiac microcirculation preventing HS-induced heart failure.
Heat stress can particularly affect the kidney because of its high rate of adenosine triphosphate consumption. Competition between apoptosis and autophagy-mediated survival always exists in damaged tissue. And Hsp90 can enhance cellular protection to resist heat stress. However, the relationship between Hsp90 and the above competition and its underlying mechanism in the kidney are unclear. The present study found that heat stress induced obvious histopathological and oxidative injury, which was connected with cellular apoptosis and autophagy in the kidney and was associated with the levels of Hsp90 expression or function. The data showed that during heat stress, Hsp90 activated the PKM2-Akt signaling pathway to exert antiapoptotic effects and induce Hsp70 expression regulated by HSF-1, stimulated autophagy-mediated survival through the HIF-1α-BNIP3/BNIP3L pathway, and finally protected the kidney from heat-stress injury. Moreover, the nuclear translocation of PKM2, (p-) Akt, HSF-1, and HIF-1α was enhanced by heat stress, but only intranuclear p-Akt and HSF-1 were specifically influenced by Hsp90, contributing to regulate the cellular ability of resisting heat-stress damage. Our study provided new insights regarding the molecular mechanism of Hsp90 in the kidney in response to heat-stress injury, possibly contributing to finding new targets for the pharmacological regulation of human or animal acute kidney injury from heat stress in future research.Autophagy, a lysosomal degradation pathway, is an essential cellular adaptation mechanism for avoiding oxidative damage. Studies of the role of autophagy in AKI have reported both beneficial and detrimental effects [12][13][14]. Light chain 3 (LC3), is essential for autophagy and serves as a vital component in monitoring autophagy and visualizing autophagosomes in vivo [15]. Pyruvate kinase M2 isoform (PKM2), a rate-limiting terminal glycolytic enzyme, catalyzes the last step of glycolysis, and recent studies have reported that PKM2 is associated with the Akt signal pathway, which regulates cell survival and apoptosis [16,17]. Meanwhile, many cellular signals have been reported to be involved in the regulation of autophagy, including the Akt (protein kinase B)-mTOR (mammalian target of rapamycin) pathway [18,19]. Furthermore, Akt also plays a vital role in resisting heat stress-induced apoptosis [20]. Hypoxia-inducible factor (HIF), especially HIF-1α, is also a major actor in the cell survival autophagy in response to hypoxia stress via BNIP3 (Bcl-2/adenovirus E1B 19-kDa interacting protein 3) and BNIP3L (Bcl-2/adenovirus E1B 19-kDa interacting protein 3 like) [21]. However, understanding the roles and their interplay of autophagy and apoptosis, and identification of the closely related signaling pathways in the kidney, is still very deficient but important for controlling tissue damage during heat stress.At the cellular level, tolerance to heat stress is mainly regulated by heat shock proteins (HSPs), which are also synthesized under various environmental and oxidative...
Outbreaks of short beak dwarf syndrome caused by novel goose parvovirus (NGPV) have been prevalent in China since 2015, resulting in a high mortality rate of ducks.Herein we evaluated differences between two NGPV strains: Muscovy duck-origin (AH190917-RP: MD17) and Cherry Valley duck-origin (JS191021-RP: CVD21) NGPV.Both of them showed certain level of pathogenicity to primary duck embryo fibroblasts, Cherry Valley duck embryos and ducklings. CVD21 showed comparatively stronger pathogenicity than MD17. Only CVD21 caused obvious cytopathic effect (CPE), characterized by cell shedding; further, the virus titer of MD17 and CVD21 was 10 2.571 ELD 50 (i.e. median embryo lethal dose)/0.2 ml and 10 6.156 ELD 50 /0.2 ml, respectively, and the mortality rate of CVD21-and MD17-infected Cherry Valley ducklings was 100% and 80%, respectively. In addition, CVD21 had a greater influence on the growth and development of ducklings. Furthermore, we found that MD17 could infect Muscovy duck embryos and produce lesions similar to Cherry Valley duck embryos, but it could not infect Muscovy duck embryo fibroblasts (MDEFs,) and Muscovy ducklings.MDV21 had no infection to MDEFs, Muscovy duck embryo and Muscovy ducklings. We then sequenced the complete genome of the two isolates to enable genomic characterization. The complete genome of MD17 and CVD21 was 5046 and 5050 nucleotides in length, respectively. Nucleotide alignment, amino acid analysis and phylogenetic tree analysis revealed that MD17 showed higher homology to goose parvovirus (GPV), while CVD21 demonstrated stronger similarity with NGPV. Moreover, the two isolates shared 95.8% homology, with encoded proteins showing multiple amino acid variations. Our findings indicate that Muscovy ducks seem to have played a crucial role in the evolution of GPV to NGPV. We believe that our data should serve as a foundation for further studying the genetic evolution of waterfowl parvoviruses and their pathogenic mechanisms.
Tilmicosin is widely used to treat respiratory infections in animals and has been reported to induce cardiac damage and even sudden death. However, its exact mechanisms, especially in chickens, remain unclear. This study confirmed the dose-dependent damaging effect of tilmicosin on primary chicken myocardial cells. Primary chicken myocardial cells treated with tilmicosin (0.5 μg/mL) for 0 h, 12 h, and 48 h were subjected to RNA sequencing and bioinformatics analysis. Transcriptomic analysis revealed that cytokine-cytokine receptor interactions, calcium signaling pathway, peroxisomes, phagosomes, mitogen-activated protein kinase ( MAPK ) signaling pathway, and oxidative phosphorylation were significantly and differentially affected after 12 h or 48 h of tilmicosin treatment. Further evidence demonstrated consistently increased proinflammatory factors, peroxidation, and ferroptosis, and intracellular ion imbalance was caused by tilmicosin for 12 h, but this imbalance had recovered at 48 h. Meanwhile, intracellular resistance to tilmicosin-induced toxicity involved the active regulation of cyclooxygenase-1 and ATPase H + /K + –transporting beta subunit at 48 h, sustained activation of MAPK12, and downregulation of dual specificity phosphatase 10 at 12 h. In summary, this study suggests that tilmicosin exerts its cardiotoxicity in primary chicken myocardial cells through multiple mechanisms and finds several intracellular molecular targets to resist the toxicity.
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