A new poly(I:C)-decorated PLGA-PEG nanoparticle promotes Mycobacterium tuberculosis fusion protein to induce comprehensive immune responses in mice intranasally.

Protein-based subunit vaccine against tuberculosis (TB) is regarded as safer but with lower immunogenicity. To investigate effective adjuvant to improve the immunogenicity of TB subunit vaccine, we modified ploy(I:C) onto PLGA-PEG copolymer nanoparticle with polydopamine to produce a new nanoparticle adjuvant named "PLGA-PEG-poly(I:C)" (NP). M. tuberculosis fusion proteins Mtb10.4-HspX and ESAT-6-Rv2626c (M4) were encapsulated in the nanoparticles to produce the NP/M4 subunit vaccine. The PLGA-PEG/M4 nanoparticle was 200.21 ± 1.07 nm in diameter, and the polydispersity index (PDI) was 0.127 ± 0.02. Following modification with poly(I:C) by polydopamine, the NP/M4 was administered to C57BL/6 female mice intranasally and the immune responses were evaluated. The NP/M4 significantly induced antigen-specific CD4+ T cells proliferation, IL-2 and IFN-γ production. In addition, the NP/M4 could promote the production of antigen-specific IgG, IgG1, IgG2c in serum, and sIgA in lung washings. Overall, our results indicated that the NP would be a potential TB subunit vaccine adjuvant with the ability to induce strong Th1-type cell-mediated immunity and humoral immune responses.

Synergism therapeutic and immunoregulatory effects of Albendazole + rAd-mIL-28B against Echinococcosis in experiment-infected mice with protoscoleces.

The metacestode stage of Echinococcus granulosus can cause cystic echinococcosis (CE), which still widely occurs around the world. Since the early 1970s, benzimidazoles have been shown to inhibit the growth of cysts and used to treat CE. However, benzimidazoles are still ineffective in 20%-40% of cases. In order to explore the new agents against CE, we have investigated the therapeutic effect of the recombinant adenoviral vector expressing mouse IL-28B (rAd-mIL-28B) on protoscoleces-infected mice. In our study, we successfully established the model mice which infected with protoscoleces intraperitoneally. At 18 weeks post-infection, the mice received rAd-mIL-28B (1×107 PFU) weekly by intramuscular injection for 6 weeks. Compared with the untreated control (13.1 ± 2.2 g), there was a significant reduction in cysts wet weight in rAd-mIL-28B group (8.3 ± 3.5 g) (P < 0.05), especially in Albendazole (ABZ) + rAd-mIL-28B group (5.8 ± 1.4 g) (P < 0.01). We also observed the severe damage of the germinal layer and the laminated layer of cysts after treatment. rAd-mIL-28B group showed a prominent increase in the level of Th1 type cytokines (such as IFN-γ, IL-2 and TNF-α). Meanwhile, the frequency of Foxp3+ T cells was decreased in the rAd-mIL-28B group (4.83 ± 0.81%) and ABZ + rAd-mIL-28B group (4.60 ± 0.51%), comparing with the untreated group (8.13 ± 2.60%) (P < 0.05). In addition, compared with the untreated control (122.14 ± 81.09 pg/ml), the level of IFN-γ significantly increased in peritoneal fluid in the rAd-mIL-28B group (628.87 ± 467.16 pg/ml) (P < 0.05) and ABZ + rAd-mIL-28B group (999.76 ± 587.60 pg/ml) (P < 0.001). Taken together, it suggested that ABZ + IL-28B may be a potential therapeutic agent against CE.

Characterization and Recombinant Genotypes of HIV-1 in Gansu Province, China.

It is important to monitor the diversity and evolution of HIV-1 genotypes, especially in some remote and undeveloped regions in China where the diversity and distribution of HIV-1 genotypes are not fully clear. To investigate the genotypes and distribution of HIV-1 in far Northwestern Gansu Province of China, we selected 220 HIV-1-positive plasma samples from the Center for Disease Control and Prevention (CDC) in Gansu from January 2016 to December 2018. The viral load of inclusion samples were over 1,000 copies per milliliter. The gag, pol, and env gene of HIV-1 were amplified by nested reverse transcription-polymerase chain reaction kit, sequenced, and then identified genotypes using HIV-BLAST tool and the neighbor-joining method. One hundred fifty of 220 inclusion samples were successfully determined HIV-1 genotypes. Our results show that circulating recombinant forms (CRF) 07_BC and CRF01_AE are predominant and accounted for 46.7% and 28.0%, respectively. Other HIV-1 subtypes and genotypes included B/B' (6.0%), CRF08_BC (4.0%), and C (1.3%). In addition, we reported CRF65_cpx and CRF55_01B subtypes in Gansu for the first time. Phylogenetic tree analysis showed that the sequences of different samples are scattered in different genotype groups, and no obvious aggregation occurs. Our results indicate the genetic variety and complexity of HIV-1 and provide critical information for HIV/AIDS control and prevention in Gansu Province.

Nutrition and exercise interventions could ameliorate age-related cognitive decline: a meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effect of nutrition combined physical exercise interventions on age-related cognitive decline by a systematic review and meta-analysis. METHODS: We searched 9 databases, including PubMed, EMbase, The Cochrane Library, Web of Science, Science Direct, China National Knowledge Infrastructure (CNKI), VIP Information, China Biological Medical Database (CBM) and Wanfang for studies published until the end of December 2019. The selected trials should meet the following criteria, study objects: healthy adults aged 65 and over with cognitive dysfunction or diagnosed as MCI, but not meet the diagnostic criteria for dementia as well as no restriction on follow-up time, race or gender. Study interventions: multiple interventions including nutrition and exercise. EXCLUSION CRITERIA: (1) studies included elderly people with any type of dementia or patients with cognitive impairment induced by secondary causes, including drug, alcohol, severe organic brain diseases, mental disorders. (2) Republished literature. (3) Studies with significant differences in baseline data between groups. (4) The data in the study cannot be converted into the required data format. We reviewed and extracted information and assessed the risk of bias of recruited studies independently. Meta-analysis was performed using STATA v.15.1 software. The bias of publication was estimated by Egger test. RESULTS: A total of six RCTs representing 1039 participates were included in our meta-analysis. In terms of global cognitive function that has been assessed by neuropsychological test in different combinations, the result showed that the beneficial effect of nutrition combined exercise interventions was statistically significant [SMD = 0.23, 95% CI (0.1, 0.36), P = 0.0004]. There were no statistical differences from assays on MMSE scores, Memory, Executive Function, Attention, and Information Processing Speed across groups. CONCLUSIONS: The current study shows that nutrition combined exercise interventions can improve global cognitive function in the aged with cognitive decline. Further researches emphasizing on longer follow-up time, experimental randomness, credibility and scale would better elucidate the effect of nutrition combined exercise interventions on cognitive function, particularly in older adults. (registration number: CRD42020159291, date of registration: 28/04/2020).

Prevalence of Different Genotypes of HIV-1 in Injection Drug Users in China: A Systematic Review and Meta-Analysis.

BACKGROUND: Since 1981, an increasing trend in HIV has been observed for transmission via injection drug users (IDUs), sexual transmission and mother-to-child transmission. The IDUs are blamed for early increases in HIV-positive cases in China. OBJECTIVE: HIV genotypes of IDUs were comprehensively analysed to trace the source and relationships of the AIDS epidemic in China. METHODS: Relevant databases written in English and Chinese were searched. Overall, 7,149 publications were identified in six databases. After screening 7,104 articles according to the inclusion and exclusion criteria, 45 studies consisting of 2,765 cases were finally identified. A meta-analysis was conducted using R MATLAB software, RevMan and SPSS. Subgroup analyses focused on time frame, region, and location of different genotypes of IDUs in China. RESULTS: There were five dominant HIV-1 genotypes among the 2,765 IDU cases. The proportions of CRF07_BC, CRF01_AE, CRF08_BC, subtype B/B', and subtype C were 45.18% (95% CI: 33.55-57.08%), 16.00% (95% CI: 9.39-23.82%), 13.43% (95% CI: 7.32-20.84%), 3.58% (95% CI: 1.52-6.24%), and 0.90% (95% CI: 0.04-2.43%), respectively. HIV genotypes transmitted among IDUs in China are primarily CRF07-BC, followed by CRF01-AE and CRF08-BC. Across the different time frames and regions, CRF07_BC was the most prevalent HIV-1 genotype among IDUs, while CRF08_BC was the most prevalent genotype in the southwest region. CONCLUSION: Our study reveals that CRF07-BC was the dominant prevalent strain among IDUs from 1991 to 2015 in China, while CRF08-BC was the dominant prevalent strain among IDUs in southwestern China. This systematic review and meta-analysis shows evidence of the comprehensive prevalence of different genotypes, data and characteristics of HIV among IDUs in China.