Search

Mumps virus (MuV) is a highly contagious human pathogen and frequently causes worldwide outbreaks despite available vaccines. Similar to other mononegaviruses such as Ebola and rabies, MuV uses a single-stranded negative-sense RNA as its genome, which is enwrapped by viral nucleoproteins into the helical nucleocapsid. The nucleocapsid acts as a scaffold for genome condensation and as a template for RNA replication and transcription. Conformational changes in the MuV nucleocapsid are required to switch between different activities, but the underlying mechanism remains elusive due to the absence of high-resolution structures. Here, we report two MuV nucleoprotein-RNA rings with 13 and 14 protomers, one stacked-ring filament and two nucleocapsids with distinct helical pitches, in dense and hyperdense states, at near-atomic resolutions using cryo-electron microscopy. Structural analysis of these in vitro assemblies indicates that the C-terminal tail of MuV nucleoprotein likely regulates the assembly of helical nucleocapsids, and the C-terminal arm may be relevant for the transition between the dense and hyperdense states of helical nucleocapsids. Our results provide the molecular mechanism for structural plasticity among different MuV nucleocapsids and create a possible link between structural plasticity and genome condensation. Shan et al. describes the high-resolution structures of Nucleoprotein in two different oligomeric states and four different higher-order helical structures. They further describe the structural rearrangements required to transition between the different helical assemblies obtained, highlighting the basis for structural plasticity among different MuV nucleocapsids. [ABSTRACT FROM AUTHOR]

Inorganic dietary nitrate plays vital roles in biological functions via the exogenous NO3-/NO2-/NO pathway under hypoxia and ischemia. We previously verified the antioxidative effects of inorganic nitrate in a mouse model of total body irradiation (TBI). Accordingly, in this study, we evaluated the effects of inorganic nitrate on prevention of TBI-induced colon injury and dysbiosis of the gut microbiome. Nitrate significantly rescued the abnormal biological indexes (body weight, white blood cell, red blood cell, platelet, hemoglobin level and intestinal canal lengths) induced by TBI. Then, we detected oxidative stress and DNA damage indexes (phospho-histone H2AX and p53 binding protein 1), which were both increased by irradiation (IR) and alleviated by nitrate. IR-induced apoptosis and senescence were ameliorated by inorganic nitrate. The distribution of the gut microbiome differed for mice with TBI and those receiving inorganic nitrate. The average abundance of Lactobacillus significantly increased, and that of Bacteroidales decreased at the genus level in the nitrate group compared with that in the IR alone group. At 30 days after TBI, the abundances of Bacteroides and Faecalibaculum decreased, whereas that of Lactobacillus increased in the IR + nitrate group compared with that in the IR alone group. Inorganic nitrate efficiently prevents TBI-induced colon epithelium injury and maintains the homeostasis of the gut microbiome. Thus, our results showed that inorganic nitrate might be a promising treatment for TBI induced colon injury. Image 1 • We evaluated the effects of inorganic nitrate on TBI-induced colon injury prevention. • Nitrate significantly rescued the abnormal biological indexes induced by TBI. • Oxidative stress and DNA damage were increased by IR and reduced by nitrate. • The gut microbiome differed for mice with TBI and those receiving inorganic nitrate. • Inorganic nitrate prevented TBI-induced colon epithelium injury. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) involves chronic inflammation, loss of epithelial integrity, and gastrointestinal microbiota dysbiosis. Effective therapies for IBD have not been established. Accordingly, in this study, we evaluated the effects of inorganic nitrate, a potent nitric oxide (NO) donor and microbiota regulator, in a mouse model of dextran sodium sulfate (DSS)-induced colitis. Mice were pretreated with NaNO 3 (2 mM) in their drinking water for 5 days, and NaCl was used as a control. Feces were collected for microbiota analyses. The results showed that oral administration of dietary nitrate could maintained colon consistency, improved colon length, maintained body weight, decreased apoptosis in colon epithelial cells, and ameliorated inflammatory cell infiltration in both the colon and peripheral blood. Microbiota profiling revealed that nitrate regulated dysbiosis. Analysis of the top bacteria at the genus level showed that Bacteroidales_S24-7_group_unidentified , Lactobacillus , Bacteroides , and Prevotellaceae_UCG-001 decreased in the DSS group compared with that in the normal group, whereas Lactobacillus , Ruminococcaceae_UCG-014 , and Prevotellaceae_UCG-001 were increased in the DSS + NaNO 3 group compared with that in the DSS group. The enriched bacteria in the nitrate group included Gordonibacter , Ureaplasama , and Lachnospiraceae_UCG-006. Moreover, microbiota analysis revealed that nitrate could partially decrease the enriched metabolic pathways (p53 signaling pathway and colorectal cancer pathway) compared with that in the DSS and DSS + NaCl groups. Overall, these findings indicated that nitrate could ameliorate DSS-induced colitis by decreasing inflammation, reducing apoptosis, and regulating the microbiota by activation of the NO 3 −/NO 2 −/NO pathway. Nitrate might be a potential treatment for colitis patients in the future clinical application. Inflammatory bowel disease (IBD) which was characterized by impaired colon epithelium and dysbiosis of gut microbiome, has emerged as a public health challenge worldwide. Inorganic nitrate efficiently alleviated the symptoms of experimental mouse DSS induced colitis via activating the NO 3 −/NO 2 −/NO pathway. The potentially mechanism were via ameliorating inflammatory cell infiltration, regulating microbiota dysbiosis and restoring beneficial bacteria. Image 1 • We evaluated the effect of nitrate on DSS-induced colitis in mice. • Dietary nitrate ameliorated inflammatory cell infiltration in the colon and PB. • Nitrate regulated microbiota dysbiosis and restored beneficial bacteria in the gut. • Nitrate ameliorated DSS-induced colitis by activation of the NO 3 −/NO 2 −/NO pathway. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the protective effect of inorganic nitrate against systemic damage in a mouse model of total body gamma irradiation (TBI).Methods and Materials: C57BL/6 mice in the irradiation (IR) + NaNO3 group were pretreated with 2 mmol/L NaNO3 in their drinking water for 1 week before receiving 5 Gy irradiation. Animals that received only 5 Gy irradiation were designated as the IR group. Survival and body weight were monitored. The peripheral blood lymphocytes, heart, liver, lung, and submandibular gland were harvested and assessed. Reactive oxygen species (ROS) were measured in the lung and submandibular gland. We examined phosphorylated histone H2AX (p-H2AX) and p53-binding protein 1 (53BP1) as markers of early-stage DNA damage and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Bax/caspase 3 mRNA expression as markers of apoptosis.Results: No improvement of survival was observed in the IR + NaNO3 group after TBI, but body weight loss after 5 Gy TBI was significantly attenuated in the IR + NaNO3 group. The levels of peripheral blood erythrocytes, leukocytes, and platelets at 7 days postirradiation recovered with nitrate treatment; moreover, the p-H2AX level in the peripheral blood lymphocytes was much lower in the IR + NaNO3 group at 2 and 4 hours post irradiation. In the lung and submandibular gland, the levels of p-H2AX, 53BP1 and ROS as well as TUNEL staining were significantly decreased in the IR + NaNO3 group compared with those in the IR group. Gene expression of Bax and caspase 3 was decreased in both the lung and submandibular gland with nitrate treatment, indicating attenuation of apoptosis.Conclusion: Inorganic nitrate delivery could effectively prevent TBI-induced systemic damage. Nitrate-mediated decreases in ROS levels may contribute to this systemic protective effect. [ABSTRACT FROM AUTHOR]

Promising vaccine adjuvants of self-assembling peptide hydrogels for protein ovalbumin (OVA) are introduced in this study. The hydrogels are formed by the enzyme of phosphatase, and the vaccine adjuvant potency of both L- and D-peptide hydrogels is evaluated. The results indicate that, compared with the clinically used alum adjuvant, both L- and D-peptide hydrogels can increase the IgG production of OVA for about 1.3 and 3.8 times, respectively. Both gels can enhance antigen uptake and induce dendritic cell maturation, and promote and prolong accumulation of antigen in lymph node, as well as evoke germinal center formation. However, the D-peptide hydrogel with OVA exhibits a slightly more efficient accumulation of OVA in the lymph nodes and seems preventing tumor growth more significantly than its L-counterpart. With the good biocompatibility and degradability of peptide hydrogels, the hydrogels described in this study have big potential for the production of protein vaccines for immunotherapy against different diseases. [ABSTRACT FROM AUTHOR]

We report an efficient strategy for intracellular protein delivery by co-assembled supramolecular nanofibers of peptides and proteins. [ABSTRACT FROM AUTHOR]