BackgroundMicroRNAs are stable and easy to detect in plasma. The plasma levels of microRNAs are often changed in disease conditions, including cancer. This makes circulating microRNAs a novel class of biomarkers for cancer diagnosis. Analyses of online microRNA data base revealed that expression level of three microRNAs, microRNA-24 (miR-24), microRNA-320a (miR-320a), and microRNA-423-5p (miR-423-5p) were down-regulated in colorectal cancer (CRC). However, whether the plasma level of these three microRNAs can serve as biomarkers for CRC diagnosis and prognosis is not determined.MethodsPlasma samples from 223 patients with colorectal related diseases (111 cancer carcinoma, 59 adenoma, 24 colorectal polyps and 29 inflammatory bowel disease) and 130 healthy controls were collected and subjected to reverse transcription-quantitative real time PCR (RT-qPCR) analyses for the three microRNAs. In addition, plasma samples from 43 patients were collected before and after surgical treatment for the same RT-qPCR analyses.ResultsThe concentrations of plasma miR-24, miR-320a and miR-423-5p were all decreased in patients with CRC and benign lesions (polyps and adenoma) compared with healthy controls, but increased in inflammatory bowel disease (IBD). The sensitivity of miR-24, miR-320a and miR-423-5p for early stage of CRC were 77.78 %, 90.74 %, and 88.89 %, respectively. Moreover, the plasma concentration of the three microRNAs was increased in patients after the surgery who had clinical improvement.ConclusionsThe plasma levels of miR-24, miR-320a, and miR-423-5p have promising potential to serve as novel biomarkers for CRC detection, especially for early stage of CRC, which are superior to the currently used clinical biomarkers for CRC detection, such as CEA and CA19-9. Further efforts to develop the three microRNAs as biomarkers for early CRC diagnosis and prediction of surgical treatment outcomes are warrant.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0198-6) contains supplementary material, which is available to authorized users.

BackgroundA vaccine against coronavirus disease 2019 (COVID-19) with highly effective protection is urgently needed. The anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody response and duration after vaccination are crucial predictive indicators.ObjectivesTo evaluate the response and duration for 5 subsets of anti-SARS-CoV-2 antibodies after vaccination and their predictive value for protection.MethodsWe determined the response and duration for 5 subsets of anti-SARS-CoV-2 antibodies (neutralizing antibody, anti-RBD total antibody, anti-Spike IgG, anti-Spike IgM, and anti-Spike IgA) in 61 volunteers within 160 days after the CoronaVac vaccine. A logistic regression model was used to determine the predictors of the persistence of neutralizing antibody persistence.ResultsThe seropositivity rates of neutralizing antibody, anti-RBD total antibody, anti-Spike IgG, anti-Spike IgM, and anti-Spike IgA were only 4.92%, 27.87%, 21.31%, 3.28% and 0.00%, respectively, at the end of the first dose (28 days). After the second dose, the seropositivity rates reached peaks of 95.08%, 100.00%, 100.00%, 59.02% and 31.15% in two weeks (42 days). Their decay was obvious and the seropositivity rate remained at 19.67%, 54.10%, 50.82%, 3.28% and 0.00% on day 160, respectively. The level of neutralizing antibody reached a peak of 149.40 (101.00–244.60) IU/mL two weeks after the second dose (42 days) and dropped to 14.23 (7.62–30.73) IU/mL at 160 days, with a half-life of 35.61(95% CI, 32.68 to 39.12) days. Younger participants (≤31 years) had 6.179 times more persistent neutralizing antibodies than older participants (>31 years) (P<0.05). Participants with anti-Spike IgA seropositivity had 4.314 times greater persistence of neutralizing antibodies than participants without anti-Spike IgA seroconversion (P<0.05).ConclusionsAntibody response for the CoronaVac vaccine was intense and comprehensive with 95.08% neutralizing seropositivity rate, while decay was also obvious after 160 days. Therefore, booster doses should be considered in the vaccine strategies.

BackgroundDue to anti-SARS-CoV-2 antibody decay and SARS-CoV-2 variants, vaccine booster doses are a constant concern. It was focused on whether the third dose can quickly evoke and activate immunity and produce a sufficient and durable immune protection.ObjectivesTo evaluate the responses and durations of five subsets of anti-SARS-CoV-2 antibodies and their predictive values for protection after the administration of a three-dose inactivated SARS-CoV-2 vaccines regimens.MethodsA prospective cohort study of five subsets of anti-SARS-CoV-2 antibodies (neutralizing antibody, anti-RBD total antibody, anti-Spike IgG, anti-Spike IgM, and anti-Spike IgA) was carried out to evaluate the efficacies and immune characteristics of a three-dose inactivated SARS-CoV-2 vaccines regimen in 32 volunteers. The dynamic response and immune decay were longitudinally profiled at 18 serial time points over 368 days.ResultsThe neutralizing antibody, anti-RBD total antibody, anti-Spike IgG and anti-Spike IgA levels rapidly increased to 773.60 (380.90-1273.00) IU/mL, 639.30 (399.60-878.60) AU/mL, 34.48 (16.83-44.68) S/CO and 0.91 (0.35-1.14) S/CO, respectively, after the administration of the third dose. Compared to the peak value after the second dose, these values were increased by 4.22-fold, 3.71-fold, 1.01-fold and 0.92-fold. On the other hand, the half-lives of the neutralizing antibody, anti-RBD total antibody, and anti-Spike IgG were 56.26 (95% CI, 46.81 to 70.49) days, 66.37 (95% CI, 54.90 to 83.88) days, and 82.91 (95% CI, 63.65 to 118.89) days, respectively. Compared to the half-lives after the second dose, these values were increased by 1.71-fold, 2.00-fold, and 2.93-fold, respectively. Nevertheless, the positive conversion rate of anti-Spike IgM was decreased to 9.38% (3/32), which was much lower than that after the second dose (65.63% (21/32)).ConclusionsCompared to the second dose, the third dose dramatically increased the antibody levels and decay times. However, the half-life of neutralizing antibody remained unsatisfactory. Due to decay, a fourth dose, and even annual revaccination, might be considered in the SARS-CoV-2 vaccination management strategy.

BackgroundThe inflammasome responses in Treponema pallidum infection have been poorly understood to date. This study aimed to investigate the expression of the nucleotide-binding leucine-rich receptor protein 3 (NLRP3) inflammasome in the development of tissue inflammation in rabbits infected with T. pallidum.MethodsForty-five rabbits were randomly assigned to a blank group or an infection group, and the latter was divided into no benzathine penicillin G (BPG) and BPG treatment subgroups. Rabbits in the infection group were injected intradermally with 0.1 mL of a 107/mL T. pallidum suspension at 10 marked sites along the back, and the blank group was treated with normal saline. The BPG treatment subgroup received 200,000 U of BPG administered intramuscularly twice, at 14 d and 21 d post-infection. The development of lesions was observed, and biopsies of the injection site and various organs, including the kidney, liver, spleen, lung, and testis, were obtained for NLRP3, caspase-1, and interleukin-1β (IL-1β) mRNA analysis during infection. Blood was also collected for the determination of IL-1β concentration.ResultsRabbits infected with T. pallidum (both the BPG treatment and no BPG treatment subgroups), exhibited NLRP3 inflammasome activation and IL-1β secretion in cutaneous lesions, showing a trend in elevation to decline; NLRP3 mRNA expression reached a peak at 18 d in the BPG treatment subgroup and 21 d in the no BPG treatment subgroup and returned to “normal” levels [vs. the blank group (P > 0.05)] at 42 d post-infection. The trend was similar to the change in cutaneous lesions in the infected rabbits, which reached a peak at 16 d in the BPG treatment subgroup and 18 d in the no BPG treatment subgroup. NLRP3, caspase-1, and IL-1β mRNA expression levels were slightly different in different organs. NLRP3 inflammasome activation was also observed in the kidney, liver, lung, spleen and testis. IL-1β expression was observed in the kidney, liver, lung and spleen; however, there was no detectable level of IL-1β in the testes of the infected rabbits.ConclusionsThis study established a clear link between NLRP3 inflammasome activation and the development of tissue inflammation in rabbits infected with T. pallidum. BPG therapy imperceptibly adjusted syphilitic inflammation.