Astragalus Polysaccharide improves immunogenicity of influenza vaccine as well as modulate gut microbiota in BALB/c mice.

BACKGROUND: Vaccination is the best way to prevent influenza virus infection, and insufficient antibodies make it difficult to resist influenza virus invasion. Astragalus Polysaccharide (APS) has a boosting effect on immunity, so we evaluate the effect of APS as an immune adjuvant for H1N1 influenza vaccines in this study. METHODS: The mice were immunized twice with influenza A (H1N1) vaccine and APS. Subsequently, the serum antibody levels were assessed using enzyme-linked immunosorbent assay (ELISA). The frequency of peripheral immune T cells was determined by flow cytometry. Following this, the immunized mice were exposed to a lethal dose of the virus, and changes in body weight and survival rates were recorded. Hematoxylin-eosin staining was employed to observe pathological alterations in lung and intestinal tissues. Western blot analysis was conducted to detect the expression of intestinal barrier function proteins (Occludin and Claudin-1). ELISA was utilized to measure the expression level of serum inflammatory cytokine TNF-α. Fresh mouse feces were collected after the initial immunization as well as after viral infection for 16S rRNA analysis aimed at detecting alterations in gut microbiota. RESULTS: Compared to the Hemagglutinin (HA) group, the APS group demonstrated higher levels of immunoglobulin G (IgG), IgG1, and IgG3, as well as neutralizing antibody levels. Additionally, it increased the frequency of CD8+ cells to enhance resistance against lethal infection. On day 14 post-infection, the high-dose APS group exhibited a higher survival rate (71.40 %) compared to the HA group (14.28 %), along with faster weight recovery. Furthermore, APS was found to ameliorate alveolar damage in lung tissue and rectify intestinal structural disorder. It also upregulated the expression levels of tight junction proteins Occludin and Claudin-1 in intestinal tissue while reducing serum TNF-α expression levels. In addition, populations of Colidextribacter, Peptococcaceae, and Ruminococcaceae were the dominant gut microbiota in the APS group after viral infection. CONCLUSION: APS has an immune-enhancing effect and is expected to be a novel adjuvant in the H1N1 influenza vaccine.

Ginsenoside Rb1 enhanced immunity and altered the gut microflora in mice immunized by H1N1 influenza vaccine.

Background: Influenza is an acute infectious respiratory disease caused by the influenza virus that seriously damages human health, and the essential way to prevent influenza is the influenza vaccine. Vaccines without adjuvants produce insufficient specific antibodies and therefore require adjuvants to boost antibody titers. Microbes and hosts are a community that needs to "promote bacteria," which could provide new value for the immune effect. Methods: (1) The H1N1 influenza vaccine, in combination with Ginsenoside Rb1, was co-injected into mice intraperitoneally (I.P.). Then, immunoglobulin G and antibody subtype levels were tested by enzyme-linked immunosorbent assay (ELISA). Moreover, mice were infected with a lethal dose of the H1N1 influenza virus (A/Michigan/45/2015), and survival status was recorded for 14 days. Lung tissues were stained by hematoxylin and eosin (H&E), and ELISA detected inflammatory factor expression levels. (2) Mice were immunized with Ginsenoside Rb1 combined with quadrivalent influenza inactivated vaccine(IIV4), and then IgG levels were measured by ELISA. (3) Fresh stool was collected for fecal 16S rDNA analysis. Results: Ginsenoside Rb1 boosted IgG and antibody subtypes in the H1N1 influenza vaccine, improved survival of mice after virus challenge, attenuated lung histopathological damage, and reduced inflammatory cytokines expression in IL-6 and TNF-α. The results of 16S rDNA showed that Rb1 decreased species diversity but increased species richness compared to the PBS group and increased the abundance of Akkermansiaceae and Murbaculaceae at the Family and Genus levels compared with the HA+Alum group. Conclusion: Ginsenoside Rb1 has a boosting effect on the immune efficacy of the H1N1 influenza vaccine and is promising as a novel adjuvant to regulate the microecological balance and achieve an anti-infective effect.

Diagnostic value of combined detection of CA72-4, CA19-9, and carcinoembryonic antigen comparing to CA72-4 alone in gastric cancer: a systematic review and meta-analysis.

Background: Gastric cancer (GC) is one of the most common malignant tumors in humans. Carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and CA72-4 are all serum tumor markers for diagnosis of gastric cancer. However, the results of studies reporting the diagnosis of the combined three varied. In this study, the combined diagnostic performance of these 3 serum tumor markers was systematically evaluated. Methods: PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang data were searched for literature on serum tumor markers CEA, CA19-9, and CA72-4 in the diagnosis of gastric cancer. The inclusion criteria were designed according to the Participants, Intervention, Control, Outcomes, Study (PICOS) principles. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) scoring scale was used to assess the quality of the literature. After extracting the data, Stata 16.0 software was used for meta-analysis. Results: A total of 10 articles were finally included, and a total of 6,574 patients participated in diagnosis, 3,077 for confirmed GC and 3,497 for non-GC respectively. Meta-analysis results showed that the diagnostic sensitivity of the combined diagnosis of the 3 tumor markers was 0.67 [95% confidence interval (CI): 0.54, 0.77], the specificity was 0.89 (95% CI: 0.82, 0.93), the positive likelihood ratio was 5.9 (95% CI: 3.5, 9.8), the negative likelihood ratio was 0.38 (95% CI: 0.27, 0.53), and the diagnostic odds ratio (DOR) was 16 (95% CI: 8, 32). The diagnostic sensitivity of CA72-4 diagnosis alone was 0.58 (95% CI: 0.40, 0.73), specificity was 0.86 (95% CI: 0.80, 0.90), the positive likelihood ratio was 4.0 (95% CI: 3.1, 5.1), the negative likelihood ratio was 0.49 (95% CI: 0.34, 0.71), and the DOR was 8 (95% CI: 5, 14). The area under the ROC curve (AUC) values of the combined three diagnosis and CA72-4 diagnosis alone were 0.87 (95% CI: 0.83, 0.89) and 0.84 (95% CI: 0.81, 0.87), respectively, the difference was statistically significant (Z=4.86, P<0.05). Discussion: The combined use of the 3 tumor markers has higher sensitivity and specificity than single marker diagnosis in the diagnosis of gastric cancer.

Analysis of Gut Microbiota in Patients with Coronary Artery Disease and Hypertension.

Cardiovascular and cerebrovascular diseases are characterized by high rates of morbidity and mortality. Microbiota is closely associated with cardiovascular disease. We aimed to comprehensively analyze the microbiotas of 300 healthy controls, 300 patients with high blood pressure (HBP), and 300 patients with coronary heart disease (CHD). The results indicated no significant difference in microbiota diversity among the three groups (P > 0.05). However, differences in microbiota richness among the three groups were significant (P < 0.05). Bacteroidetes and Bacteroidia were the dominant bacteria in the CHD group, Enterobacteriales and Escherichia-shigella in the HBP group, and Acidaminococcaceae and Phascolarctobacterium in the healthy control group. The prediction results of the random forest model indicated that the population with CHD displayed prominent features with high sensitivity, indicating that microbiota detection might become a novel clinical indicator to predict and monitor the risk of cardiovascular events. The prediction of microbiota function suggested differences in oxygen supply and chronic inflammation between populations with HBP/CHD and healthy populations. Although there is no difference in gut microbiota diversity among the three groups, each group has its dominant microbiota in terms of richness.