Unlocking the antiviral potential of rosmarinic acid against chikungunya virus via IL-17 signaling pathway.

Background: The Chikungunya virus is an Alphavirus that belongs to the Togaviridae family and is primarily transmitted by mosquitoes. It causes acute infection characterized by fever, headache, and arthralgia. Some patients also experience persistent chronic osteoarthritis-like symptoms. Dedicated antiviral treatments are currently unavailable for CHIKV. This study aims to explore the potential anti-CHIKV effect of rosmarinic acid using network pharmacology. Methods: This study employed network pharmacology to predict and verify the molecular targets and pathways associated with ROSA in the context of CHIKV. The analysis outcomes were further validated using molecular docking and in vitro experiments. Results: The analysis of CHIKV targets using the Kyoto Encyclopedia of Genes and Genomes and MCODE identified IL-17 as an important pathogenic pathway in CHIKV infection. Among the 30 targets of ROSA against CHIKV, nearly half were found to be involved in the IL-17 signaling pathway. This suggests that ROSA may help the host in resisting CHIKV invasion by modulating this pathway. Molecular docking validation results showed that ROSA can stably bind to 10 core targets out of the 30 identified targets. In an in vitro CHIKV infection model developed using 293T cells, treatment with 60 µM ROSA significantly improved the survival rate of infected cells, inhibited 50% CHIKV proliferation after CHIKV infection, and reduced the expression of TNF-α in the IL-17 signaling pathway. Conclusion: This study provides the first confirmation of the efficacy of ROSA in suppressing CHIKV infection through the IL-17 signaling pathway. The findings warrant further investigation to facilitate the development of ROSA as a potential treatment for CHIKV infection.

Retrospective investigation of the origin and epidemiology of the dengue outbreak in Yunnan, China from 2017 to 2018.

Since 2013, a dengue epidemic has broken out in Yunnan, China and neighboring countries. However, after the COVID-19 pandemic in 2019, the number of dengue cases decreased significantly. In this retrospective study, epidemiological and genetic diversity characterizations of dengue viruses (DENV) isolated in Yunnan between 2017 and 2018 were performed. The results showed that the dengue outbreak in Yunnan from 2017 to 2018 was mainly caused by DENV1 (genotype I and genotype V) and DENV2 (Asia I, Asia II, and Cosmopolitan). Furthermore, correlation analysis indicated a significant positive correlation between the number of imported and local cases (correlation coefficient = 0.936). Multiple sequence alignment and phylogenetic divergence analysis revealed that the local isolates are closely related to the isolates from Myanmar and Laos. Interestingly, recombination analysis found that the DENV1 and DENV2 isolates in this study had widespread intra-serotype recombination. Taken together, the results of the epidemiological investigation imply that the dengue outbreak in Yunnan was primarily due to imported cases. This study provides a new reference for further investigations on the prevalence and molecular epidemiology of DENV in Yunnan, China.

Marein ameliorates diabetic nephropathy by inhibiting renal sodium glucose transporter 2 and activating the AMPK signaling pathway in db/db mice and high glucose-treated HK-2 cells.

Marein, an active component of the Coreopsis tinctoria Nutt. plant, is known to improve diabetic nephropathy (DN). However, its anti-diabetic functions in DN and potential mechanisms remain unclear. The aim of this study was to elucidate the effects and mechanisms of Marein in diabetic db/db mice with DN, and in high glucose-treated HK-2 cells. In vivo, treating diabetic db/db mice with Marein for 12 consecutive weeks restored diabetes-induced hyperglycemia and dyslipidemia, and ameliorated renal function deterioration, glomerulosclerosis, and renal ectopic lipid deposition. Marein exerted renoprotective effects by directly inhibiting renal tubule sodium glucose transporter 2 (SGLT2) expression, and then activating the AMP-activated protein kinase (AMPK)/acetyl CoA carboxylase (ACC)/peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) pathway in db/db mice. Meanwhile, Marein ameliorated fibrosis and inflammation by suppressing the pro-inflammatory factors interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1), and expression of the extracellular matrix proteins, fibronectin (FN) and collagen 1 (COL1) in diabetic mice. In vitro, MDCK monolayer cells were established to explore the characteristics of Marein transmembrane transport. Marein was found to be absorbed across the membrane at a medium level that involved active transport and this was mediated by SGLTs. In HK-2 cells, Marein decreased uptake of the fluorescent glucose analog, 2-NBDG, by 22 % by inhibiting SGLT2 expression. In high glucose-treated HK-2 cells, Marein decreased SGLT2 expression and increased phosphorylated (p)-AMPK/p-ACC to improve high glucose-induced cellular dysfunction. Furthermore, Marein treatment decreased SGLT2 expression in SGLT2-overexpressing HK-2 cells. In addition, molecular docking and dynamics analysis revealed that SGLT2 was a direct target of Marein. Collectively, our results demonstrated that Marein ameliorates DN by inhibiting renal SGLT2 and activating p-AMPK, suggesting Marein can potentially prevent DN by suppressing renal SGLT2 expression directly.

An epidemiological investigation of porcine circovirus 3 infection in dogs in the Guangxi Province from 2015 to 2017, China.

Porcine circovirus type 3 (PCV3) is an emerging circovirus species associated with several diseases. The study aimed to investigate the frequency of porcine circovirus 3 (PCV3) and its coinfection with canine parvovirus type 2 (CPV-2) in dogs in the Guangxi province from 2015 to 2017, China, and to examine the genome diversity of PCV3. Using polymerase chain reaction (PCR) amplification and sequencing, 96 of 406 (23.6%)samples were positive for PCV3, 38 out of 406 (9.4%) samples were coinfected with both PCV3 and CPV-2. The CPV-positive rate was significantly higher in the PCV3-positive samples than in the non-PCV3 samples, and the difference was extremely significant (P < 0.01). The complete genome (n=4) and ten capsid genes (n=10) of PCV3 were sequenced. Multiple sequence alignment results showed that these sequences shared 98.5-100% nucleotide similarity with the reference genome sequence and 97.5-100% nucleotide similarity with the reference capsid gene sequence. PCV3 was classified into two different genotypes, according to phylogenetic analysis based on the whole genome. These strains were clustered in PCV3a, showing a close relationship with PCV3-US/SD2016. Surprisingly, we separately analyzed these PCV3 strains from the Guangxi province and found that the dog and pig PCV3 are from different branches. In summary, this was the first seroprevalence and genetic investigation of PCV3 in dogs in the Guangxi province, China, and the first complete genome PCV3 from dogs obtained in the world. The results provide insights into the epidemiology and pathogenesis of this important virus.

Sequence and phylogenetic analysis of novel porcine parvovirus 7 isolates from pigs in Guangxi, China.

Parvoviruses are a diverse group of viruses that infect a wide range of animals and humans. In recent years, advances in molecular techniques have resulted in the identification of several novel parvoviruses in swine. In this study, porcine parvovirus 7 (PPV7) isolates from clinical samples collected in Guangxi, China, were examined to understand their molecular epidemiology and co-infection with porcine circovirus type 2 (PCV2). In this study, among the 385 pig serum samples, 105 were positive for PPV7, representing a 27.3% positive detection rate. The co-infection rate of PPV7 and PCV2 was 17.4% (67/385). Compared with the reference strains, we noted 93.9%-97.9% similarity in the NS1 gene and 87.4%-95.0% similarity in the cap gene. Interestingly, compared with the reference strains, sixteen of the PPV7 strains in this study contained an additional 3 to 15 nucleotides in the middle of the cap gene. Therefore, the Cap protein of fourteen strains encoded 474 amino acids, and the Cap protein of the other two strains encoded 470 amino acids. However, the Cap protein of the reference strain PPV7 isolate 42 encodes 469 amino acids. This is the first report of sequence variation within the cap gene, confirming an increase in the number of amino acids in the Cap protein of PPV7. Our findings provide new insight into the prevalence of PPV7 in swine in Guangxi, China, as well as sequence data and phylogenetic analysis of these novel PPV7 isolates.