Long-lasting humoral and cellular memory immunity to vaccinia virus Tiantan provides pre-existing immunity against mpox virus in Chinese population.

Investigating immune memory to vaccinia virus and pre-existing immunity to mpox virus (MPXV) among the population is crucial for the global response to this ongoing mpox epidemic. Blood was sampled from vaccinees inoculated with vaccinia virus Tiantan (VTT) strain born before 1981 and unvaccinated control subjects born since 1982. After at least 40 years of the inoculation, 60% or 5% VTT vaccinees possess neutralizing antibodies (NAbs) to VTT or MPXV, with at least 50% having T cell memory to VTT protein antigens. Notably, 46.7% vaccinees show pre-existing T cell responses to MPXV. Broad pre-existing CD8+ T cell reactivities to MPXV are detected not only against conserved epitopes but also against variant epitopes between VTT and MPXV. Persistent NAbs and T cell memory to VTT among vaccinees, along with pre-existing T cells to MPXV among both vaccinees and the unvaccinated population, indicate a particular immune barrier to mpox.

Secretogranin III may be an indicator of paraquat-induced astrocyte activation and affects the recruitment of BDNF during this process.

Astrocyte activation has been described as a multi­stage defensive response, which is characterized by the morphological alteration of astrocytes and the overexpression of intermediate filament proteins. However, the functional mechanism of the secretion system in activated astroglia remains unclear. It has previously been demonstrated that secretogranin II, a member of the granin family, may be involved in the sorting and expression of inflammatory factors and excitatory neurotransmitters in paraquat (PQ)­induced astroglial activation. Secretogranin III (SCG3) has been reported to represent an important component of the regulated secretory pathway in neuroendocrine cells; however, its role as an anchor protein of dense­core vesicles in astrocytes remains to be elucidated. In the present study, a PQ­activated U118MG astrocytoma cell model established in our previous study was used to investigate the effects of SCG3. The results revealed that SCG3 was highly expressed and subsequently released from cells in response to PQ. Inhibition of SCG3 expression via transfection with small interfering RNA partially restored astrocyte morphology, but did not affect the expression of astrocytic factors. Further studies investigating the association between SCG3 and other cellular factors were conducted, in order to determine the expression levels and subcellular localization of these proteins. Neurotrophins and inflammatory factors exhibited an increase in characteristic expression patterns, paralleling the alterations in SCG3 expression. The results further demonstrated that brain­derived neurotrophic factor partially colocalized with SCG3­positive vesicles; however, the localization of interleukin­6 was not affected. In conclusion, SCG3 may be involved in PQ­induced astrocyte activation via regulation of the expression and selective recruitment of cellular factors, thus suggesting that SCG3 may represent an indicator of astrocyte activation.

Effects of PQ's cytotoxicity on secretory vesicles in astroglia: Expression alternation of secretogranin II and its potential interaction with intracellular factors.

It has been extensively characterized that paraquat (PQ) selectively targets to the substantia nigra and exerts neurotoxic actions on dopaminergic neurons. However, a little knowledge is available about astroglia in PQ exposure, especially its complex secretory machinery. To explore this point, we built up a PQ-induced model in cultural U118 astrocyte. Since the granin family is considered as a master regulator of cargo sorting and large dense core vesicles (LDCVs) biogenesis in the regulated secretory pathway of nervous and neuroendocrine cells, the current study focused on one member, secretogranin II (SCG2) and investigated its alternation and potential relationship with other astrocyte-derived factors under PQ insult. We found that PQ upregulated SCG2 expression on both RNA and protein levels and stimulated the mRNA expression of neurotrophic factors, cytokines and glutamine synthetase (GS) simultaneously. RNAi knockdown of SCG2 did not rescue the cell cycle arrest induced by PQ but affected expressions of IL-6 and GS on mRNA and protein levels. Further studies on subcellular location showed that SCG2-positive secretory granules were partially colocalized with IL-6 but not GS in PQ exposure astrocyte. Taken together, our findings indicate that the expression alternation of SCG2 under astroglial activation by PQ may be necessary compensation for cargo sorting and LDCV biogenesis. The involvement of the IL-6 and GS suggests that the SCG2 may potentially regulate inflammatory factors and excitatory neurotransmitter to the cytotoxicity of PQ on astroglia.

Genetic analysis of indel markers in three loci associated with Parkinson's disease.

The causal mutations and genetic polymorphisms associated with susceptibility to Parkinson's disease (PD) have been extensively described. To explore the potential contribution of insertion (I)/deletion (D) polymorphisms (indels) to the risk of PD in a Chinese population, we performed genetic analyses of indel loci in ACE, DJ-1, and GIGYF2 genes. Genomic DNA was extracted from venous blood of 348 PD patients and 325 age- and sex-matched controls without neurodegenerative disease. Genotyping of the indel loci was performed by fragment length analysis after PCR and DNA sequencing. Our results showed a statistically significant association for both allele X (alleles without 5) vs. 5 (odds ratio = 1.378, 95% confidence interval = 1.112-1.708, P = 0.003) and genotype 5/X+X/X vs. 5/5 (odds ratio = 1.681, 95% confidence interval = 1.174-2.407, P = 0.004) in the GIGYF2 locus; however, no significant differences were detected for the ACE and DJ-1 indels. After stratification by gender, no significant differences were observed in any indels. These results indicate that the GIGYF2 indel may be associated with increased risk of PD in northern China.

Female genetic distribution bias in mitochondrial genome observed in Parkinson's Disease patients in northern China.

Genetic polymorphisms associated with susceptibility to Parkinson's disease (PD) have been described in mitochondrial DNA (mtDNA). To explore the potential contribution of mtDNA mutations to the risk of PD in a Chinese population, we examined the linkage relationship between several single nucleotide polymorphisms (SNPs) and haplotypes in mtDNA and PD. We genotyped 5 SNPs located on coding genes using PCR-RFLP analysis. A specific allele 10398G demonstrated an increased risk of PD (OR 1.30; 95% CI 0.95-1.76; P = 0.013). After stratification by gender, the increased risk appeared to be more significant in females (OR 1.91; 95% CI 1.16-3.16; P = 0.001). But the significance only appeared in females under Bonferroni correction. No significant differences were detected for other SNPs (T4336C, G5460A, G9055A, and G13708A). Individual haplotype composed of 4336T-5460G-9055G-10398A-13708G was found to be associated with protective effect regarding PD (P = 0.0025). The haplotypes 4336T-5460G-9055G-10398G-13708G and 4336T-5460G-9055G-10398A-13708G were more significantly associated in females (P = 0.0036 for risk and P = 0.0006 for protective effects). These data suggest that the A10398G and two haplotypes coupled with 10398A or 10398G are closely associated with susceptibility to PD in a northern Chinese population. This association demonstrated a female genetic distribution bias.