SARS-CoV-2 causes the recent global COVID-19 public health emergency. ACE2 is the receptor for both SARS-CoV-2 and SARS-CoV. To predict the potential host range of SARS-CoV-2, we analyzed the key ...residues of ACE2 for recognizing S protein. We found that most of the selected mammals including pets (dog and cat), pangolin and Circetidae mammals remained the most of key residues for association with S protein from SARS-CoV and SARS-CoV-2. The interaction interface between cat/dog/pangolin/Chinese hamster ACE2 and SARS-CoV/SARS-CoV-2 S protein was simulated through homology modeling. We identified that N82 in ACE2 showed a closer contact with SARS-CoV-2 S protein than M82 in human ACE2. Our finding will provide important insights into the host range of SARS-CoV-2 and a new strategy to design an optimized ACE2 for SARS-CoV-2 infection.
•Pets (dog and cat), pangolin and Circetidae remained the key residues for association with S from SARS-CoV and SARS-CoV-2.•The interface of the interaction between cat/dog/pangolin/Chinese hamster ACE2 and SARS-CoV/SARS-CoV-2 RBD was simulated.•N82 of ACE2 showed a closer contact with SARS-CoV-2 S than M82, suggesting an optimized ACE2 for SARS-CoV-2 infection.
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causes the recent COVID‐19 public health crisis. Bat is the widely believed original host of SARS‐CoV‐2. However, its intermediate host ...before transmitting to humans is not clear. Some studies proposed pangolin, snake, or turtle as the intermediate hosts. Angiotensin‐converting enzyme 2 (ACE2) is the receptor for SARS‐CoV‐2, which determines the potential host range for SARS‐CoV‐2. On the basis of structural information of the complex of human ACE2 and SARS‐CoV‐2 receptor‐binding domain (RBD), we analyzed the affinity to S protein of the 20 key residues in ACE2 from mammal, bird, turtle, and snake. Several ACE2 proteins from Primates, Bovidae, Cricetidae, and Cetacea maintained the majority of key residues in ACE2 for associating with SARS‐CoV‐2 RBD. The simulated structures indicated that ACE2 proteins from Bovidae and Cricetidae were able to associate with SARS‐CoV‐2 RBD. We found that nearly half of the key residues in turtle, snake, and bird were changed. The simulated structures showed several key contacts with SARS‐CoV‐2 RBD in turtle and snake ACE2 were abolished. This study demonstrated that neither snake nor turtle was the intermediate hosts for SARS‐CoV‐2, which further reinforced the concept that the reptiles are resistant against infection of coronavirus. This study suggested that Bovidae and Cricetidae should be included in the screening of intermediate hosts for SARS‐CoV‐2.
Research Highlights
Affinities to SARS‐CoV‐2 S protein of the 20 key residues in ACE2 from mammal, bird, turtle and snake were analyzed.
ACE2 proteins from Primates, Bovidae, Cricetidae and Cetacea were predicted to associate with SARS‐CoV‐2 RBD.
Neither snake nor turtle was the intermediate hosts for SARS‐CoV‐2
MicroRNAs (miRNAs) have been implicated in the regulation of milk protein synthesis and development of the mammary gland (MG). However, the specific functions of miRNAs in these regulations are not ...clear. Therefore, the elucidation of miRNA expression profiles in the MG is an important step towards understanding the mechanisms of lactogenesis.
Two miRNA libraries were constructed from MG tissues taken from a lactating and a non-lactating Holstein dairy cow, respectively, and the short RNA sequences (18-30 nt) in these libraries were sequenced by Solexa sequencing method. The libraries included 885 pre-miRNAs encoding for 921 miRNAs, of which 884 miRNAs were unique sequences and 544 (61.5%) were expressed in both periods. A custom-designed microarray assay was then performed to compare miRNA expression patterns in the MG of lactating and non-lactating dairy cows. A total of 56 miRNAs in the lactating MG showed significant differences in expression compared to non-lactating MG (P<0.05). Integrative miRNA target prediction and network analysis approaches were employed to construct an interaction network of lactation-related miRNAs and their putative targets. Using a cell-based model, six miRNAs (miR-125b, miR-141, miR-181a, miR-199b, miR-484 and miR-500) were studied to reveal their possible biological significance.
Our study provides a broad view of the bovine MG miRNA expression profile characteristics. Eight hundred and eighty-four miRNAs were identified in bovine MG. Differences in types and expression levels of miRNAs were observed between lactating and non-lactating bovine MG. Systematic predictions aided in the identification of lactation-related miRNAs, providing insight into the types of miRNAs and their possible mechanisms in regulating lactation.
Scope
Dietary supplementation with polyphenol‐rich propolis can protect against experimentally induced colitis. We examined whether different polyphenol compositions of Chinese propolis (CP) and ...Brazilian propolis (BP) influence their ability to protect against dextran sulfate sodium (DSS)‐induced colitis in rats.
Methods and results
HPLC‐DAD/Q‐TOF‐MS analysis confirmed that polyphenol compositions of CP and BP were dissimilar. Rats were given CP or BP by gavage (300 mg kg−1 body weight) throughout the study, starting 1 week prior to DSS treatment for 1 week followed by 3 d without DSS. CP and BP significantly reduced the colitis disease activity index relative to controls not receiving propolis, prevented significant DSS‐induced colonic tissue damage, and increased resistance to DSS‐induced colonic oxidative stress as shown by reduced malonaldehyde levels and increased T‐AOC levels. CP and BP significantly reduced DSS‐induced colonic apoptosis. Colonic inflammatory markers IL‐1β, IL‐6, and MCP‐1 were suppressed by CP and BP, whereas only BP‐induced expression of TGF‐β. CP, not BP, increased the diversity and richness of gut microbiota populations. Both forms of propolis significantly reduced populations of Bacteroides spp.
Conclusions
Despite the dissimilar polyphenol compositions of CP and BP, their ability to protect against DSS‐induced colitis is similar. Nevertheless, some different physiological impacts were observed.
Propolis is an important hive product with abundant polyphenols. Here, it is shown that despite the dissimilar polyphenol compositions of Chinese and Brazilian propolis, their abilities to protect against dextran sulfate sodium–induced colitis are similar. It is also demonstrated that reduced populations of Bacteroides spp. by propolis are important for maintaining gut hemostasis.
Galangin is a natural flavonoid that has been reported to provide substantial health benefits. Nevertheless, little is known about the potential effects of galangin against inflammatory bowel ...diseases. Here, an in vivo study was performed to investigate the preventive effects of galangin against dextran sulphate sodium (DSS)-induced acute murine colitis, which mimics the symptoms of human ulcerative colitis (UC). Pre-treatment with galangin (15 mg/kg,
) resulted in a significant decreased in the macroscopic signs of DSS-induced colitic symptoms, including a decreased disease activity index, prevention of the colon length shortening, and alleviation of the pathological changes occurring in the colon. Colonic pro-inflammatory mediators, including tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6, as well as myeloperoxidase activities were decreased following galangin pre-treatment when compared with the DSS control group. Moreover, galangin pre-treatment significantly increased the expressions of autophagy-related proteins and promoted the formation of autophagosome in the colon. Galangin pre-treatment increased the diversity of the gut microbiota, and this was accompanied by increased levels of short-chain fatty acids. These observed changes could involve the modulating effects conferred by galangin in relation to some specific bacteria populations, including the recovery of
spp., and increased
spp. Overall, these results support the use of galangin in the prevention of UC.
Recently, the NLRP3 inflammasome activation in the eyes has been known to be associated with the pathogenesis of age-related macular degeneration. The aim of this study was to investigate the ...protective effects of cyanidin-3-glucoside (C3G), an important anthocyanin with great potential for preventing eye diseases, against 4-hydroxyhexenal- (HHE-) induced inflammatory damages in human retinal pigment epithelial cells, ARPE-19. We noticed that C3G pretreatment to the ARPE-19 cells rescued HHE-induced antiproliferative effects. Cell apoptosis ratio induced by HHE was also decreased by C3G, measured by flow cytometry. The activation of NLRP3 inflammasome induced by HHE was found with increases of caspase-1 activity, proinflammatory cytokine releases (IL-1β and IL-18), and NLRP3 inflammasome-related gene expressions (NLRP3, IL-1β, IL-18, and caspase-1). The C3G showed potent inhibitive effects on these NLRP3 inflammasome activation hallmarks induced by HHE. Moreover, we noticed that the C3G’s pretreatment leads to a delayed and a decreased JNK activation in HHE-challenged ARPE-19 cells. Finally, using a luciferase reporter gene assay system, we demonstrated that HHE-induced activation protein- (AP-) 1 transcription activity was abolished by C3G pretreatment in a dose-dependent manner. Taken together, these data showed that HHE leads to inflammatory damages to ARPE-19 cells while C3G has great protective effects, highlighting future potential applications of C3G against AMD-associated inflammation.
cAMP is a critical second messenger mediating activity-dependent neuronal survival and neurite growth. We investigated the expression and function of the soluble adenylyl cyclase (sAC, ADCY10) in CNS ...retinal ganglion cells (RGCs). We found sAC protein expressed in multiple RGC compartments including the nucleus, cytoplasm and axons. sAC activation increased cAMP above the level seen with transmembrane adenylate cyclase (tmAC) activation. Electrical activity and bicarbonate, both physiologic sAC activators, significantly increased survival and axon growth, whereas pharmacologic or siRNA-mediated sAC inhibition dramatically decreased RGC survival and axon growth in vitro, and survival in vivo. Conversely, RGC survival and axon growth were unaltered in RGCs from AC1/AC8 double knock-out mice or after specifically inhibiting tmACs. These data identify a novel sAC-mediated cAMP signaling pathway regulating RGC survival and axon growth, and suggest new neuroprotective or regenerative strategies based on sAC modulation.
Propolis has abundant polyphenolic constituents and is used widely as a health/functional food. Here, we investigated the effects of polyphenol-rich propolis extracts (PPE) on intestinal barrier ...function in human intestinal epithelial Caco-2 cells, as well as in rats. In Caco-2 cells, PPE increased transepithelial electrical resistance and decreased lucifer yellow flux. PPE-treated cells showed increased expression of the tight junction (TJ) loci occludin and zona occludens (ZO)-1. Confocal microscopy showed organized expressions in proteins related to TJ assembly, i.e., occludin and ZO-1, in response to PPE. Furthermore, PPE led to the activation of AMPK, ERK1/2, p38, and Akt. Using selective inhibitors, we found that the positive effects of PPE on barrier function were abolished in cells in which AMPK and ERK1/2 signaling were inhibited. Moreover, rats fed a diet supplemented with PPE (0.3% in the diet) exhibited increased colonic epithelium ZO-1 expression. Overall, these data suggest that PPE strengthens intestinal barrier function by activating AMPK and ERK signaling and provide novel insights into the potential application of propolis for human gut health.
The improvement of chicken growth performance is one of the major concerns for the poultry industry. Gut microbes are increasingly evidenced to be associated with chicken physiology and metabolism, ...thereby influencing chicken growth and development. Here, through integrated multi-omics analyses, we showed that chickens from the same line differing in their body weight were very different in their gut microbiota structure and host-microbiota crosstalk; microbes in high body weight (HBW) chickens contributed to chicken growth by regulating the gut function and homeostasis. We also verified that a specific bacterial consortium consisting of isolates from the HBW chickens has the potential to be used as chicken growth promoters. These findings provide new insights into the potential links between gut microbiota and chicken phenotypes, shedding light on future manipulation of chicken gut microbiota to improve chicken growth performance.
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