DNA损伤在衰老相关疾病中的研究进展

DNA损伤是衰老相关疾病领域的研究热点, 可引起细胞周期停滞、凋亡, 加快个体衰老速度、增加衰老相关疾病的患病风险。本文将从细胞衰老和个体衰老两个层面阐述其与衰老之间的研究进展, 并综述其与衰老常见相关疾病(肿瘤、心血管疾病、阿尔茨海默病)及早衰综合征的关系, 为抗衰老研究和临床干预衰老相关疾病提供理论依据。     

Evaluation of the MHSeqTyper47 kit for forensically challenging DNA samples

Microhaplotypes have been highly regarded for forensic mixture DNA deconvolution because they do not experience interference from stutters in the same way as short tandem repeat markers, and they tend to be more polymorphic than single nucleotide polymorphism markers. However, forensic microhaplotype kits have not been reported. The MHSeqTyper47 kit genotypes 47 microhaplotype loci. In this study, MiSeq FGx sequencing metrics for MHSeqTyper47 were presented, and the genotyping accuracy of this kit was examined. The sensitivity of MHSeqTyper47 reached 62.5 pg, and full genotyping results were obtained from degraded DNA samples with degradation indexes ≤ 3.00. Full genotypes were obtained in the presence of 100 ng/μL tannin, 50 μM heme, 25 ng/μL humic acid, and 1.25 μg/μL indigo dye. In DNA mixture studies, a minimum of 31 loci of the minor contributor were correctly genotyped at 1:99 or 99:1 mixing ratios, with the cumulative random matching probability of these loci reaching 4.54 × 10⁻²⁵. Mixing ratios could be reliably predicted from two-donor DNA mixtures based on the loci with four called alleles. Taken together, these data showed that the MHSeqTyper47 kit was effective for forensically challenging DNA analysis.     

多发性骨髓瘤中表观遗传学修饰的研究进展北大核心

多发性骨髓瘤(multiple myeloma,MM)是一种病因不明,目前仍无法治愈的恶性血液系统性疾病。研究显示MM是一种复杂的表观遗传学修饰所驱动的恶性肿瘤,表观遗传学修饰是改变MM发病进展的重要机制,并影响治疗及预后。本文将对表观遗传学异常调控在MM的发生发展过程中的作用及相关耐药机制和治疗的现状进行综述。     

Validation of donor fraction cell-free DNA with biopsy-proven cardiac allograft rejection in children and adults

ObjectivesDonor-specific cell-free DNA shows promise as a noninvasive marker for allograft rejection, but as yet has not been validated in both adult and pediatric recipients. The study objective was to validate donor fraction cell-free DNA as a noninvasive test to assess for risk of acute cellular rejection and antibody-mediated rejection after heart transplantation in pediatric and adult recipients.MethodsPediatric and adult heart transplant recipients were enrolled from 7 participating sites and followed for 12 months or more with plasma samples collected immediately before all endomyocardial biopsies. Donor fraction cell-free DNA was extracted, and quantitative genotyping was performed. Blinded donor fraction cell-free DNA and clinical data were analyzed and compared with a previously determined threshold of 0.14%. Sensitivity, specificity, negative predictive value, positive predictive value, and receiver operating characteristic curves were calculated.ResultsA total of 987 samples from 144 subjects were collected. After applying predefined clinical and technical exclusions, 745 samples from 130 subjects produced 54 rejection samples associated with the composite outcome of acute cellular rejection grade 2R or greater and pathologic antibody-mediated rejection 2 or greater and 323 healthy samples. For all participants, donor fraction cell-free DNA at a threshold of 0.14% had a sensitivity of 67%, a specificity of 79%, a positive predictive value of 34%, and a negative predictive value of 94% with an area under the curve of 0.78 for detecting rejection. When analyzed independently, these results held true for both pediatric and adult cohorts at the same threshold of 0.14% (negative predictive value 92% and 95%, respectively).ConclusionsDonor fraction cell-free DNA at a threshold of 0.14% can be used to assess for risk of rejection after heart transplantation in both pediatric and adult patients with excellent negative predictive value.     

The impact of the covalently closed circular DNA level on recurrence of hepatocellular carcinoma after initial hepatectomy: an analysis of patients with resolved hepatitis B virus infection

BackgroundWe assessed whether or not covalently closed circular DNA (cccDNA) levels in the background liver influence the recurrence of hepatocellular carcinoma (HCC) in patients with resolved hepatitis B virus (HBV) infection.MethodsAmong 425 patients who underwent initial hepatectomy for HCC between 2010 and 2018, a retrospective review was performed in 44 with resolved HBV infection. The clinicopathologic characteristics were analyzed for correlation with tumor recurrence. The HBV cccDNA levels were tested via a droplet digital polymerase chain reaction assay.ResultsHBV cccDNA was detected in 27 of 44 patients (61%), and the median level was 1.0 copies/1000 ng (range, 0-931.3 copies/1000 ng). Anti-HBc ≥8.9 S/CO was associated with cccDNA detection (odds ratio, 11.08; 95% confidence interval [95% CI], 2.48-49.46; P = 0.002). Twenty-eight patients (64%) developed HCC recurrence after hepatectomy. The overall 3- and 5-year recurrence-free survival rates were 45.7% and 34.3%, respectively.19 HBV cccDNA levels was not significantly associated with HCC recurrence, while the presence of multiple tumors was an independent risk fact or (hazard ratio, 6.53; 95% CI, 2.48-17.19; P < 0.001.ConclusionHBV cccDNA levels did not influence HCC recurrence after hepatectomy. Anti-HBc levels may be used as a surrogate marker for cccDNA.     

The Relationship between the Methylation of Promoter Regions of Tumor Suppressor Genes PTEN and APC with Endometrial Cancer

Background: Endometrial neoplasms is one of the most typical gynecologic diseases with harmful effects. Promoterhypermethylation is an important mechanism of the inactivation of tumor suppressor genes in endometrial neoplasms.Epigenetic changes of the PTEN and APC genes have shown to be present in various cancers. Therefore, in this study,we have investigated the association between the promoter hypermethylation of PTEN and APC genes with endometrialneoplasms. Methods: For this study, 28 patients with endometrial neoplasms as well as 22 controls were studied.Analysis of the promoter methylation regions of PTEN and APC genes were performed by Methylation-Specific PCR.Results: The frequency of PTEN and APC genes promoter methylation was 28.57% and 17.86% in tumor tissues, and11.54% and 3.85% in blood samples, respectively. We found a significant relationship between blood and tissue inPTEN methylation (p = 0.0353). Additionally, we determined a closely significant difference between normal tissueand tumor tissue of the PTEN gene (p = 0.0787) and blood and tissue samples of the APC gene in methylated promoterregions (p=0.0623). Furthermore, these results suggest that there is no significant relationship between the promotermethylation of PTEN and APC with clinical characteristics. Conclusion: DNA methylation deficiency is a well knownhighlighted factor in tumorigenesis, therefore the promoter hypermethylation of PTEN and APC can be indicated as arisk factor in endometrial neoplasms.