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The correction notice for the article "hPMSCs protects against D-galactose-induced oxidative damage of CD4+ T cells through activating Akt-mediated Nrf2 antioxidant signaling" by Yanlian Xiong, Yueming Wang, and Jiashen Zhang addresses errors in the use of gel bands in image analysis. The corrections made do not impact the overall results and conclusions of the study. The article discusses how hPMSCs alleviate oxidative damage in CD4+ T cells and the role of the Akt/GSK-3β/Fyn pathway in regulating Nrf2-regulated antioxidant genes in senescent CD4+ T cells. The authors express their apologies for any inconvenience caused by the errors. [Extracted from the article]

It is expected that serum protein biomarkers in Duchenne muscular dystrophy (DMD) will reflect disease pathogenesis, progression and aid future therapy developments. Here, we describe use of quantitative in vivo stable isotope labeling in mammals to accurately compare serum proteomes of wild-type and dystrophin-deficient mdx mice. Biomarkers identified in serum from two independent dystrophin-deficient mouse models (mdx-Δ52 and mdx-23) were concordant with those identified in sera samples of DMD patients. Of the 355 mouse sera proteins, 23 were significantly elevated and 4 significantly lower in mdx relative to wild-type mice (P-value < 0.001). Elevated proteins were mostly of muscle origin: including myofibrillar proteins (titin, myosin light chain 1/3, myomesin 3 and filamin-C), glycolytic enzymes (aldolase, phosphoglycerate mutase 2, beta enolase and glycogen phosphorylase), transport proteins (fatty acid-binding protein, myoglobin and somatic cytochrome-C) and others (creatine kinase M, malate dehydrogenase cytosolic, fibrinogen and parvalbumin). Decreased proteins, mostly of extracellular origin, included adiponectin, lumican, plasminogen and leukemia inhibitory factor receptor. Analysis of sera from 1 week to 7 months old mdx mice revealed age-dependent changes in the level of these biomarkers with most biomarkers acutely elevated at 3 weeks of age. Serum analysis of DMD patients, with ages ranging from 4 to 15 years old, confirmed elevation of 20 of the murine biomarkers in DMD, with similar age-related changes. This study provides a panel of biomarkers that reflect muscle activity and pathogenesis and should prove valuable tool to complement natural history studies and to monitor treatment efficacy in future clinical trials.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by the aberrant expression of the double homeobox 4 (DUX4) gene. The FLExDUX4 mouse model carries an inverted human DUX4 transgene which has leaky DUX4 transgene expression at a very low level. No overt muscle pathology was reported before 16 weeks. The purpose of this study is to track and characterize the FLExDUX4 phenotypes for a longer period, up to one year old. In addition, transcriptomic changes in the muscles of 2-month-old mice were investigated using RNA-seq. The results showed that male FLExDUX4 mice developed more severe phenotypes and at a younger age in comparison to the female mice. These include lower body and muscle weight, and muscle weakness measured by grip strength measurements. Muscle pathological changes were observed at older ages, including fibrosis, decreased size of type IIa and IIx myofibers, and the development of aggregates containing TDP-43 in type IIb myofibers. Muscle transcriptomic data identified early molecular changes in biological pathways regulating circadian rhythm and adipogenesis. The study suggests a slow progressive change in molecular and muscle phenotypes in response to the low level of DUX4 expression in the FLExDUX4 mice. [ABSTRACT FROM AUTHOR]

Sepsis, a systemic syndrome often culminating in multiple organ failure (MOF), poses a substantial global health threat. However, the gene expression pattern of various tissues associated with severe sepsis remains elusive. Applying the summary data-based Mendelian randomization (SMR) method, we integrated sepsis genome-wide association study (GWAS) data and expression quantitative trait loci (eQTLs) summaries. This facilitated the investigation of gene causality across 12 tissue types within 26 cohorts linked to adverse sepsis outcomes, including critical care and 28-day mortality. Additionally, trans-omics analyses, including blood transcriptome and single-cell RNA sequencing, were conducted to examine cellular origins and gene functions. The effects of ST7L on sepsis were validated in vivo and in vitro. We identified 127 genes associated with severe sepsis across diverse tissues. Cross-tissue analysis highlighted ST7L as a significant pan-tissue risk factor for severe sepsis, displaying significance across 11 tissues for both critical care sepsis (meta OR 1.19, 95 % CI: 1.14–1.25, meta p < 0.0001) and 28-day-death sepsis (meta OR: 1.22, 95 % CI: 1.17–1.27, meta p < 0.0001). Notably, independent blood single-cell RNA sequencing data showed specific expression of ST7L in dendritic cells (DCs). ST7L+ DCs were elevated in non-surviving sepsis patients and exhibited an augmented inflammatory molecular pattern compared to ST7L− DCs. Both transcription and translation level of ST7L in DCs exhibited a dose-dependent pattern with LPS. Knocking down ST7L by siRNA was sufficient to alleviate the inflammation phenotype of DCs, including inhibiting p65/NF-kB pathway and inflammatory factors. Our findings underscore ST7L as a pan-tissue risk factor for severe sepsis, specifically manifested in DCs and associated with an inflammatory phenotype. These results offer essential insights into the gene expression profiles across multiple tissues in severe sepsis, potentially identifying therapeutic targets for effective sepsis management. [ABSTRACT FROM AUTHOR]

Objective: The goal of our study was to investigate whether DRD4 gene DNA methylation played an important role in the susceptibility of Han Chinese SCZ. Methods: Using the bisulphite pyrosequencing technology, DNA methylation levels of 6 CpG dinucleotides in DRD4 CpG island were measured among 30 paranoid SCZ patients, 30 undifferentiated SCZ patients, and 30 age- and gender-matched healthy controls. Results: Strong correlation was observed among the six CpG sites (r>0.5, P<0.01), thus average methylation levels were applied thereafter. Our results indicated that there was a significant association between DRD4 methylation and the risk of SCZ (P = 0.003), although there was no significant difference in DRD4 methylation between the two SCZ subtypes (P = 0.670). A breakdown analysis by gender showed that the significant association of DRD4 methylation and SCZ was driven by males (P<0.001) but not by females (P = 0.835). DRD4 methylation was significantly associated with p300 in male SCZ patients (r = −0.543, P = 0.005) but not in female SCZ patients (r = 0.110, P = 0.599). Moreover, receiver operating characteristic (ROC) curves showed DRD4 methylation was able to predict the status of SCZ in males [area under curve (AUC) = 0.832, P = 0.002] but not in females (AUC = 0.483, P = 0.876). Finally, a further expression experiment showed that DRD4 methylation in the gene body was positively associated with gene expression, although the exact mechanism of gene regulation remained unknown for this interesting DRD4 methylation. Conclusion: The gender disparity in the DRD4 DNA methylation provides novel insights into the pathogenesis of SCZ. [ABSTRACT FROM AUTHOR]

DNA origami is an emerging technology that assembles hundreds of staple strands and one single-strand DNA into certain nanopattern. It has been widely used in various fields including detection of biological molecules such as DNA, RNA and proteins. MicroRNAs (miRNAs) play important roles in post-transcriptional gene repression as well as many other biological processes such as cell growth and differentiation. Alterations of miRNAs' expression contribute to many human diseases. However, it is still a challenge to quantitatively detect miRNAs by origami technology. In this study, we developed a novel approach based on streptavidin and quantum dots binding complex (STV-QDs) labeled single strand displacement reaction on DNA origami to quantitatively detect the concentration of miRNAs. We illustrated a linear relationship between the concentration of an exemplary miRNA as miRNA-133 and the STV-QDs hybridization efficiency; the results demonstrated that it is an accurate nano-scale miRNA quantifier motif. In addition, both symmetrical rectangular motif and asymmetrical China-map motif were tested. With significant linearity in both motifs, our experiments suggested that DNA Origami motif with arbitrary shape can be utilized in this method. Since this DNA origami-based method we developed owns the unique advantages of simple, time-and-material-saving, potentially multi-targets testing in one motif and relatively accurate for certain impurity samples as counted directly by atomic force microscopy rather than fluorescence signal detection, it may be widely used in quantification of miRNAs. [ABSTRACT FROM AUTHOR]

This study aimed to explore the prognostic value of LMX1B mRNA expression and the methylation of its CpG sites in patients with laryngeal squamous cell carcinoma (LSCC). An in-silicon analysis was performed using data from the cancer genome atlas (TCGA)-Head and Neck Squamous Carcinoma (HNSC). After screening, 112 LSCC and 10 adjacent normal tissues were identified as eligible samples for analysis. Results showed that LMX1B expression was significantly upregulated in the cancer tissues (p < 0.01) and was an independent prognostic indicator in terms of OS (HR: 1.233, 95%CI: 1.082–1.405, p = 0.002) and RFS (HR: 1.200, 95%CI: 1.002–1.438, p = 0.048). By examining the methylation profile of 55 CpG sites in LMX1B locus, we found that the promoter methylation status was irrelevant to LMX1B expression. In comparison, LMX1B expression was generally positively correlated with gene body methylation. Among the gene body CpG sites, cg13600622 methylation showed a better predictive value than LMX1B expression in terms of OS (HR: 12.363, 95%CI: 1.076–142.033, p = 0.043), while cg14204784 methylation was a better marker of shorter RFS (HR: 12.363, 95%CI: 1.076–142.033, p = 0.043). Among the known downstream genes of LMX1B, only NR4A2 expression showed a moderately negative correlation (Pearson's r = −0.54) with it in LSCC tissues. However, this correlation was inconsistent with previous publications those reported a positive correlation between them. Based on these findings, we infer that upregulated LMX1B mRNA expression had an independent prognostic value in LSCC patients. Increased gene body methylation might be an important mechanism of its upregulation. Among the gene body CpG sites, cg13600622 and cg14204784 methylation level might be better prognostic markers than LMX1B mRNA expression in terms of OS and RFS respectively. [ABSTRACT FROM AUTHOR]

Abstract: Cdk5 activity has been implicated in brain development and the regulation of many neuronal processes. Recently, the expression of p35 and Cdk5 activity has been reported in pancreatic beta cells. Decreased Cdk5 activity enhanced glucose-stimulated insulin secretion. This suggests that Cdk5 may play an important role in the regulation of insulin secretion. To further understand how Cdk5 regulates insulin secretion in glucose-stimulated pancreatic β cells, we first confirmed the presence of a low level of p35 in pancreatic Min6 cells. Next, in a time-course experiment in high glucose (25mM) we showed that endogenous p35 increased gradually accompanied by a 3-fold increase in Cdk5 activity by 16h. Insulin secretion, however, doubled after 2h followed by progressive downregulation, negatively correlated with Cdk5 activity. On the other hand, overexpression of p35 in these cells resulted in more than a three-fold increase in Cdk5 activity within 2h coupled to a 50% reduction in insulin secretion in both high and low (3mM) glucose. Most significantly, cells overexpressing p35, treated with high glucose for 4h, showed induction of p25, the p35-derived truncated fragment which hyperactivates Cdk5 in neurons. As a result, insulin secretion was inhibited and cells became apoptotic. Roscovitine or co-infection of dominant negative Cdk5 (dnCdk5) with p35 increased insulin secretion and inhibited apoptosis. These results suggest that the model for deregulation and hyperactivation of Cdk5 in neurodegeneration may apply to the pathology seen in type 2 diabetes (T2DM). It is consistent with the view that Alzheimer''s disease and T2DM are linked metabolically and pathologically by Cdk5 in a number of ways. [Copyright &y& Elsevier]

Abstract: In this study, we systematically screened the polymorphisms of the whole CYP2D6 gene in the populations of four different geographical locations in China, namely, Shanghai, Shantou, Shenyang, and Xi''an, using a sample of 100 subjects from each population. Forty-eight different polymorphisms were detected as well as 12 novel ones. One novel nonsynonymous SNP was detected, and one novel intronic SNP was revealed that might inactivate a cryptic donor site 392 nucleotides downstream of the exon 6 natural donor site. In addition, the frequencies of some polymorphisms and alleles demonstrated significant differences among the four populations. Linkage disequilibrium analysis and tag SNP selection were performed separately for each population. Haplotypes were analyzed within the selected tag SNPs. Tag SNP selection and haplotype distributions showed differences across the four populations. This is the first large-scale study to analyze polymorphisms systematically across the whole CYP2D6 gene in the Chinese Han population. [Copyright &y& Elsevier]

The aim of the study is to explore the protective effect of new gelatin (NG, Xin'ejiao in China) on hematopoietic injury caused by chemotherapy. Zebrafish, at 48 hours post fertilization (hpf), was treated with different chemotherapeutic drugs to establish the zebrafish hematopoietic damage model with reduced thrombocytes and erythrocytes. The protecting effects of NG on the thrombocytes and erythrocytes were observed, respectively, on zebrafish models. Then, the RT-PCR method was used to detect the change of mRNA level of the hematopoiesis-related cytokines scl1, c-myb, pu.1, GATA1, and runx1 genes. The results showed that 50 μg·mL−1 and 100 μg·mL−1 NG rescued and increased the thrombocytes numbers induced by vinorelbine (NVB) and chloramphenicol (CHL) and the erythrocytes numbers induced by methotrexate (MTX), doxorubicin (ADM), and mechlorethamine hydrochloride (MH) in zebrafish models. Meanwhile, the mRNA expression of scl1, c-myb, and GATA1 genes in the NG treatment group was raised compared with the MTX treatment group. Also, the mRNA expression of pu.1 and Runx1 in the NG treatment group was reduced compared with the MTX treatment group. In consequence, traditional Chinese medicine NG showed a certain degree protective effect on hematopoiesis injury induced by chemotherapy in this study, which may depend on the promotion of erythrocytes proliferation and the regulation of the hematopoietic genes level. [ABSTRACT FROM AUTHOR]

The purpose of the present study is to decode the underlying mechanism of Herba Sarcandrae that indicated antipurpuric effect and to unveil one of its primary components, flavonoids, which play an important role. An immune mediated bone marrow failure (BMF) model in mouse was established by infusion thymus suspension cells after radiation in vivo. Platelets isolated in vitro were prepared from normal mice and BMF mice, respectively. The expressions of PS, P-selectin, PAC-1, Bax, Bad, Bid, and caspase-9 were examined by flow cytometry, and alteration of morphology of platelets under different conditions was observed. Our results indicated that the number of platelets was increased by addition of total flavonoids, and some of apoptotic markers such as Bax, Bad, Bid, and Caspase-9 were downregulated. In addition, the phosphatidylserine (PS) exposure on platelets was inhibited by total flavonoids, and the expressions of PAC-1 and P-selectin were decreased. In conclusion, it is suggested that the total flavonoids of Herba Sarcandrae may inhibit the excessive platelet apoptosis through mitochondrial pathway. In addition, activation of platelets may be also involved in mediating apoptosis of platelets. [ABSTRACT FROM AUTHOR]

Abstract: Several studies have suggested the dysfunction of the GABAergic system as a risk factor in the pathogenesis of schizophrenia. In the present study, case-control association analysis was conducted in four GABAergic genes: two glutamic acid decarboxylase genes (GAD1 and GAD2), a GABAA receptor subunit β2 gene (GABRB2) and a GABAB receptor 1 gene (GABBR1). Using a universal DNA microarray procedure we genotyped a total of 20 SNPs on the above four genes in a study involving 292 patients and 286 controls of Chinese descent. Statistically significant differences were observed in the allelic frequencies of the rs187269C/T polymorphism in the GABRB2 gene (P =0.0450, χ 2 =12.40, OR=1.65) and the −292A/C polymorphism in the GAD1 gene (P =0.0450, χ 2 =14.64 OR=1.77). In addition, using an electrophoretic mobility shift assay (EMSA), we discovered differences in the U251 nuclear protein binding to oligonucleotides representing the −292 SNP on the GAD1 gene, which suggests that the −292C allele has reduced transcription factor binding efficiency compared with the 292A allele. Using the multifactor-dimensionality reduction method (MDR), we found that the interactions among the rs187269C/T polymorphism in the GABRB2 gene, the −243A/G polymorphism in the GAD2 gene and the 27379C/T and 661C/T polymorphisms in the GAD1 gene revealed a significant association with schizophrenia (P <0.001). These findings suggest that the GABRB2 and GAD1 genes alone and the combined effects of the polymorphisms in the four GABAergic system genes may confer susceptibility to the development of schizophrenia in the Chinese population. [Copyright &y& Elsevier]