Histone modifications in Duchenne muscular dystrophy: pathogenesis insights and therapeutic implications.

Duchenne muscular dystrophy (DMD) is a commonly encountered genetic ailment marked by loss-of-function mutations in the Dystrophin gene, ultimately resulting in progressive debilitation of skeletal muscle. The investigation into the pathogenesis of DMD has increasingly converged on the role of histone modifications within the broader context of epigenetic regulation. These modifications, including histone acetylation, methylation and phosphorylation, are catalysed by specific enzymes and play a critical role in gene expression. This article provides an overview of the histone modifications occurring in DMD and analyses the research progress and potential of different types of histone modifications in DMD due to changes in cellular signalling for muscle regeneration, to provide new insights into diagnostic and therapeutic options for DMD.

[Authenticity discrimination for Galli Gigerii Endothelium Corneum based on UPLC-MS/MS and peptidomics].

Peptidomics was employed to systematically analyze the characteristic peptides in Galli Gigerii Endothelium Corneum and its adulterants and establish a method for distinguishing Galli Gigerii Endothelium Corneum from its adulterants, including the gizzard membranes from ducks, geese, and pigeons. UPLC-Q-Exactive Orbitrap-MS was combined with multivariate statistical analysis to analyze the peptides in Galli Gigerii Endothelium Corneum and its adulterants. The structures of peptides were identified by pNovo combined with manual recognition of spectra, and synthetic peptide standards were used for validation. LC-MS/MS was used to optimize the sample pre-processing conditions, including the extraction procedure, extraction time, extraction solvents, and solvent volumes, for the characteristic peptide LESY in Galli Gigerii Endothelium Corneum. Multiple reaction monitoring(MRM) in the ESI~+ mode with m/z 511.24→269.11 and 511.24→243.13 as detection ions was employed for qualitative and quantitative analyses. The established UPLC-MS/MS method demonstrated good specificity, stability, and durability. The content of LESY in 16 batches of Galli Gigerii Endothelium Corneum samples ranged from 55.03 to 113.36 µg·g~(-1). Additionally, a qualitative detection method for the common peptide RDPVLVSR in adulterants was established with m/z 471.28→785.45 and 471.28→670.41 as the detection ions. This study established a convenient, rapid, and accurate detection method for the characteristic peptides in Galli Gigerii Endothelium Corneum and its adulterants. The method possesses good specificity, stability, and durability, providing a valuable reference for the identification and quality control of Galli Gigerii Endothelium Corneum and other traditional Chinese medicines derived from animal sources.

Chirality Gearing in an Achiral Cage through Adaptive Binding.

Herein we report an adaptive, achiral trithiourea molecular cage and its conformational and stereodynamics toward tricarboxylate anion binding. The cage was readily synthesized in four steps with a 44% yield for the irreversible cage-forming reaction. It possesses a flexible conformation and strongly binds 1,3,5-benzene tricarboxylate by forming a sandwich-like inclusion complex, with an affinity up to 106 M-1 in acetonitrile. Upon binding, the cage is locked in a twisted helical conformation. By incorporation of three chiral arms on the guest, a gear-like complex dominant in one given helical sense was produced. Due to the steric crowding in the helical grooves, a small change of methyl to ethyl on guest caused a striking difference on binding and chiral induction. The system thus represents a rare example of chiral induction on a flexible, achiral host and provides a decoupled model that the generation of a racemate and following chiral discrimination can be individually probed.

CT23 knockdown attenuating malignant behaviors of hepatocellular carcinoma cell is associated with upregulation of metallothionein 1.

The cancer-testis antigen 23 (CT23) gene has been reported in association with the pathogenesis and progress of hepatocellular carcinoma (HCC). However, the alterations of gene expression profiling induced by CT23 knockdown in HCC cells remains largely unknown. In this study, the RNA interfering (RNAi) method was used to silence CT23 expression in BEL-7404 cells. Microarray analysis was performed on mRNA extracted from the CT23 knockdown cells and the control cells to determine the alterations of gene expression profiles. The result showed a total of 1051 genes expressed differentially (two-fold change), including 470 genes upregulated and 581 gene downregulated in the CT23 knockdown cells. A bioinformatic analysis showed that the functional differentially expressed genes (DEGs) were linked to cell proliferation, migration, and apoptosis, and metallothionein 1 (MT1) attained the maximum enrichment scores in functional annotation, classification, and pathway analysis of DEGs. Furthermore, Western blot analysis and cell behaviors assays verified that CT23 modulates cell proliferation, migration, and apoptosis by regulating MT1 expression in HCC cells and non-neoplastic hepatocytes. In summary, downregulated CT23 gene in BEL-7404 cells might change the expressions of carcinogenesis and progression related genes in HCC by upregulating MT1 expression, which would provide insight into searching for a novel therapeutic target for HCC.

Ring chromosome formation by intra-strand repairing of subtelomeric double stand breaks and clinico-cytogenomic correlations for ring chromosome 9.

Constitutional ring chromosome 9, r(9), is a rare chromosomal disorder. Cytogenomic analyses by karyotyping, array comparative genomic hybridization (aCGH) and whole genome sequencing (WGS) were performed in a patient of r(9). Karyotyping detected a mosaic pattern of r(9) and monosomy 9 in 83% and 17% of cells, respectively. aCGH detected subtelomeric deletions of 407 kb at 9p24.3 and 884 kb at 9q34.3 and an interstitial duplication of 5.879 Mb at 9q33.2q34.11. WGS revealed double strand breaks (DSBs) at ends of 9p24.3 and 9q34.3, inverted repeats at ends of subtelomeric and 9q33.2q34.11 regions, and microhomology sequences at the junctions of this r(9). This is the first report of r(9) analyzed by WGS to delineate the mechanism of ring chromosome formation from repairing of subtelomeric DSBs. The loss of telomeres by subtelomeric DSBs triggered inverted repeats induced intra-strand foldback and then microhomology mediated synthesis and ligation, which resulted in the formation of this r(9) with distal deletions and an interstitial duplication. Review of literature found seven patients of r(9) with clinical and cytogenomic findings. These patients and the present patient were registered into the Human Ring Chromosome Registry and a map correlating critical regions and candidate genes with relevant phenotypes was constructed. Variable phenotypes of r(9) patients could be explained by critical regions and genes of DOCK8, DMRT, SMARCA2, CD274, IL33, PTPRD, CER1, FREM1 for 9p deletions, and the EHMT1 gene for 9q34 deletion syndrome. This interactive registry of r(9) could provide information for cytogenomic diagnosis, genetics counseling and clinical management.

Agkihpin, a Distinct SVTLE from the Venom of Gloydius halys Pallas: Purification, Characterization and Structure-Activity Determination.

Blood clots produced by snake-venom thrombin-like enzymes (SVTLEs) are cleared rapidly, which makes SVTLEs attractive as potential candidates for antithrombotic therapy. We isolated a SVTLE, agkihpin, from the venom of Gloydius halys Pallas. Agkihpin was confirmed to a single-chain TLE with molecular mass of 25.5 kD, pI of 7.43, optimal pH of 8.0 (hydrolyzing TAME), linked carbohydrate absent, and weak fibrinogen clotting activity. It was also found that (i) G. halys might be the latest species in SVTLEs phylogenetic tree; (ii) different level of conservation was shown among the SVTLEs from the Viperidae snakes. Some of those site may account for different activities exhibited by those SVTLEs, especially position 181, at which a fibrinogenolytic activity increase was found when a basic and larger amino acid substituted by a neutral and smaller one; (iii) an extra α-helix constructed with a 'Pro + acidic amino acid + aromatic amino acid' pattern was found in the SVTLEs from Gloydius and Agkistrodon snakes, although it does not necessarily imply an effect on the fibrinogenolytic activity of the SVTLEs. This study provided some new insight into the activity of SVTLE.

Expression, purification and characterization of a novel recombinant SVTLE, r-agkihpin-2, from Gloydius halys Pallas venom gland in Escherichia coli.

In our previous work, a thrombin-like enzyme (TLE), agkihpin, was successfully isolated, purified, cloned and named from the venom of Gloydius halys Pallas, having fibrinolytic, fibrinogenolytic and thrombosis-reduced activities, attenuating migration of liver cancer cell, and without bleeding risk. To explore the possibility of agkihpin as a thrombolytic and/or anti-metastasis agent in the future, in this study recombinant agkihpin was expressed and purified in Escherichia coli, and its biological activities investigated. Thus, r-agkihpin-2 was successfully expressed and purified and confirmed by Western blot and peptide mass fingerprinting. After purification and renaturation, 46 mg (399 U) of active r-agkihpin-2 was obtained from 1 L bacterial culture. The results of the arginine esterase activity assay, fibrin plate test fibrinogenolytic activity assay, thrombin-induced venous thrombosis assay, Scratch-Wound assay and bleeding assay showed that active r-agkihpin-2 had slightly lower TAME hydrolytic, fibrinolytic, fibrinogenolytic, thrombus-reduced and migration-attenuated activities than those of native agkihpin, and had no bleeding risk. These findings confirmed that, active r-agkihpin-2 could be further investigated for thrombolytic and/or anti-metastasis drug discovery in the future.

Beyond a tumor suppressor: Soluble E-cadherin promotes the progression of cancer.

E-cadherin (E-cad) plays important roles in tumorigenesis as well as in tumor progression, invasion and metastasis. This protein exists in two forms: a membrane-tethered form and a soluble form. Full-length E-cad is membrane tethered. As a type I transmembrane glycoprotein, E-cad mainly mediates adherens junctions between cells and is involved in maintaining the normal structure of epithelial tissues. Soluble E-cad (sE-cad) is the extracellular fragment of the protein that is cleaved from the membrane after proteolysis of full-length E-cad. The production of sE-cad undermines adherens junctions, causing a reduction in cell aggregation capacity; furthermore, sE-cad can diffuse into the extracellular environment and the blood. As a paracrine/autocrine signaling molecule, sE-cad activates or inhibits multiple signaling pathways and participates in the progression of various types of cancer, such as breast cancer, ovarian cancer, and lung cancer, by promoting invasion and metastasis. This article briefly reviews the role of sE-cad in tumorigenesis and tumor progression and its significance in clinical therapeutics.

Agkihpin, a novel SVAE may inhibit the migration and invasion of liver cancer cells associated with the inversion of EMT induced by Wnt/ß-catenin signaling inhibition.

In our previous work, agkihpin, a snake venom arginine esterase (SVAE), was isolated from the Gloydius halys Pallas, which could attenuate the migration of liver cancer cells. However, the mechanism of the effect of agkihpin on attenuating migration of liver cancer cell is unknown yet. Here, to learn more about agkihpin and explore the possibility of agkihpin as an anti-metastatic drug in the future, a series of experiments about the migration and invasion of liver cancer cells with agkihpin, HepG 2 and SMMC-7721, was conducted. Epithelial-mesenchymal transition (EMT) is an initial step and a major phenotype of cancer metastasis and invasion, while a number of EMT opposite phenomenons were observed, for example, epithelial marker E-cadherin was up-regulated, mesenchymal markers N-cadherin and Vimentin, and transcription regulators Snail and twist were down-regulated after treating with agkihpin in liver cancer cells; canonical Wnt/ß-catenin pathway, one of the signals initiated EMT, was inhibited by decreased expressions of FZD7 and ß-catenin, phosphorylation of GSK3ß (Ser9), and nuclear ß-catenin accumulation in agkihpin treated cancer cells. By using bioinformatics analysis and protease activity analysis in vitro we also found that agkihpin might bind and degrade FZD7. As a result, we hypothesized that agkihpin could inhibit the Wnt/ß-catenin signaling pathway by cleaving FZD7, leading to the inactivation of the TCF/LEF transcription factor, which contributed to the inversion of EMT, and finally attenuated the migration and invasion of liver cancer cells. Therefore, our findings provided novel mechanistic insights into the role of SVAEs in liver cancer controlling, and raised the possibility that agkihpin may be used therapeutically in liver cancer.

Cloning, expression, and partial characterization of FBPA from Schistosoma japonicum, a molecule on that the fluke may develop nutrition competition and immune evasion from human.

Carbohydrate metabolism is the most important physiological process for Schistosoma japonicum which resides in host. However, as a key glycolytic enzyme in carbohydrate metabolism, fructose-1,6-bisphosphate aldolase (FBPA), there is no study on its enzymatic kinetics and antigenic peptides. Here, we report the gene cloning, expression, purification, and kinetics of the FBPA from S. japonicum (sjFBPA). After cloning, sjFBPA gene was introduced into pET-28a and transformed BL21, and a soluble His6-sjFBPA was expressed and purified successfully at the expected molecular mass of ~45 kDa. We first reported that the diversities in IGS regions and the features of residues position 346 and 357-362 of sjFBPA may be conferred either through conformational changes influencing easily the active site from a distance and/or causing the C-terminal region to interact directly with the active site, which lead His6-sjFBPA to exhibit a higher specific activity of 197.43 units/mg and degrades FBP with a typical substrate inhibition model and a higher efficiency of k cat = 6261.3/s and K m = 0.061 µM than human aldolases, which might be the strategy that S. japonicum gaining energy and surviving in its environment with low concentration of carbohydrate, and benefitting to get more metabolic substances for parasites in nutrition competition with their host. sjFBPA exhibits a high similarity of 81.46 % with that of hosts, especially in antigenic peptide regions, and 14 of 15 antigenic peptides of sjFBPA were conserved to those of human aldolase A, B, and/or C with high identity (17, 16, or 16 antigenic peptides, respectively), which may result in a molecular mimicry of FBPA with that of host, and an immune evasion from their hosts. This work would supply an experimental base for using FBPA to prevent the schistosomiasis in the future.

Integrated exome sequencing and microarray analyses detected genetic defects and underlying pathways of hepatocellular carcinoma.

We performed whole exome sequencing (WES) and microarray analysis to detect somatic variants and copy number alterations (CNAs) for underlying mechanisms in a case series of hepatocellular carcinoma (HCC) with paired DNA samples from tumor and adjacent nontumor tissues. Clinicopathologic findings based on Edmondson-Steiner (E-S) grading, Barcelona-Clinic Liver Cancer (BCLC) stages, recurrence, and survival status and their associations with tumor mutation burden (TMB) and CNA burden (CNAB) were evaluated. WES from 36 cases detected variants in the TP53, AXIN1, CTNNB1, and SMARCA4 genes, amplifications of the AKT3, MYC, and TERT genes, and deletions of the CDH1, TP53, IRF2, RB1, RPL5, and PTEN genes. These genetic defects affecting the p53/cell cycle control, PI3K/Ras, and ß-catenin pathways were observed in approximately 80% of cases. A germline variant in the ALDH2 gene was detected in 52% of the cases. Significantly higher CNAB in patients with poor prognosis by E-S grade III, BCLC stage C, and recurrence than patients with good prognosis by grade III, stage A, grade III and nonrecurrence was noted. Further analysis on a large case series to correlate genomic profiling with clinicopathologic classifications could provide evidence for diagnostic interpretation, prognostic prediction, and target intervention on involved genes and pathways.

[Haplotype analysis for mucocutaneous venous malformations in a Chinese Han ethnic family].

A Chinese Han ethnic family with mucocutaneous venous malformations (VMCM) was investigated. This family has autosomal dominantly inherited VMCM in five generations, and the offspring has a 50% risk of this inherited disorder. Affected individuals have small, spongy, and multiple vascular lesions, which often locate in the skin, oral mucosa, and upper and lower extremities. None of the family members had gastrointestinal bleeding, central nervous system involvement and cardiac defects. Pathological analysis showed that the veins have irregular vascular space and walls with variable thickness. All phenotypes of the patients displayed the basic characters of VMCM. To analyze the genetic locus and haplotype, genomic DNA of 26 family members was obtained from peripheral leukocytes, and the linkage analysis and haplotypes analysis were performed using microsatellites markers. The results of two-point linkage analysis and haplotype analysis showed that the disease-causing gene located within a 7 cM region between D9S1121 and D9S161 on the short arm of chromosome 9. The study firstly reported the Chinese family with VMCM, which disease-causing gene is located in 9p, consistent with western VMCM families reported. Four flanking markers, D9S1121, D9S169, D9S16 and D9S248, were used to define the linkage haplotypes in the family, which can provide useful informaion for researchers to study VMCM in different racial background.

Electroacupuncture Activates Neuroplasticity in the Motor Cortex and Corticospinal Tract via the mTOR Pathway in a Rat P-MCAO Model.

Electroacupuncture (EA) combines traditional Chinese medicine acupuncture theory with modern scientific technology. It is a promising therapy for the treatment of cerebrovascular diseases such as cerebral infarction. A large number of clinical studies have shown that EA promotes recovery of neurological function after cerebral infarction, however, the underlying mechanisms behind its effects remain unclear. We tested whether EA stimulation of the Zusanli (ST36) and Neiguan (PC6) acupoints activates neuroplasticity in rats with ischemic stroke and whether this involves the regulation of axonal regeneration through the mTOR pathway. 24 h after permanent middle cerebral artery occlusion (p-MCAO) in rats, EA treatment was started for 20 min, daily, for 14 days. We found that EA significantly reduced Modified Neurological Severity Scores (mNSS), cerebral infarct volume, and apoptosis of neuronal cells. EA also significantly increased the expression of the neuroplasticity-associated proteins GAP-43 and SYN and upregulated the phosphorylation levels of AKT, mTOR, S6, and PTEN to promote CST axon sprouting in the spinal cord at C1-C4 levels. The positive effects of EA were blocked by the administration of the mTOR inhibitor Rapamycin. In short, we found that EA of the Zusanli (ST36) and Neiguan (PC6) acupoints in p-MCAO rats induced neuroprotective and neuroplastic effects by regulating the mTOR signaling pathway. It promoted neuroplasticity activated by axon regeneration in the contralateral cortex and corticospinal tract. Activation of such endogenous remodeling is conducive to neurological recovery and may help explain the positive clinical effects seen in patients with infarcts.

The past, present, and future for constitutional ring chromosomes: A report of the international consortium for human ring chromosomes.

Human ring chromosomes (RCs) are rare diseases with an estimated newborn incidence of 1/50,000 and an annual occurrence of 2,800 patients globally. Over the past 60 years, banding cytogenetics, fluorescence in situ hybridization (FISH), chromosome microarray analysis (CMA), and whole-genome sequencing (WGS) has been used to detect an RC and further characterize its genomic alterations. Ring syndrome featuring sever growth retardation and variable intellectual disability has been considered as general clinical presentations for all RCs due to the cellular losses from the dynamic mosaicism of RC instability through mitosis. Cytogenomic heterogeneity ranging from simple complete RCs to complex rearranged RCs and variable RC intolerance with different relative frequencies have been observed. Clinical heterogeneity, including chromosome-specific deletion and duplication syndromes, gene-related organ and tissue defects, cancer predisposition to different types of tumors, and reproductive failure, has been reported in the literature. However, the patients with RCs reported in the literature accounted for less than 1% of its occurrence. Current diagnostic practice lacks laboratory standards for analyzing cellular behavior and genomic imbalances of RCs to evaluate the compound effects on patients. Under-representation of clinical cases and lack of comprehensive diagnostic analysis make it a challenge for evidence-based interpretation of clinico-cytogenomic correlations and recommendation of follow-up clinical management. Given recent advancements in genomic technologies and organized efforts by international collaborations and patient advocacy organizations, the prospective of standardized cytogenomic diagnosis and evidence-based clinical management for all patients with RCs could be achieved at an unprecedented global scale.

Unknown Disease Outbreaks Detection: A Pilot Study on Feature-Based Knowledge Representation and Reasoning Model.

Background: The outbreak of COVID-19 in 2019 has rapidly swept the world, causing irreparable loss to human beings. The pandemic has shown that there is still a delay in the early response to disease outbreaks and needs a method for unknown disease outbreak detection. The study's objective is to establish a new medical knowledge representation and reasoning model, and use the model to explore the feasibility of unknown disease outbreak detection. Methods: The study defined abnormal values with diagnostic significances from clinical data as the Features, and defined the Features as the antecedents of inference rules to match with knowledge bases, achieved in detecting known or emerging infectious disease outbreaks. Meanwhile, the study built a syndromic surveillance base to capture the target cases' Features to improve the reliability and fault-tolerant ability of the system. Results: The study combined the method with Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and early COVID-19 outbreaks as empirical studies. The results showed that with suitable surveillance guidelines, the method proposed in this study was capable to detect outbreaks of SARS, MERS, and early COVID-19 pandemics. The quick matching accuracies of confirmed infection cases were 89.1, 26.3-98%, and 82%, and the syndromic surveillance base would capture the Features of the remaining cases to ensure the overall detection accuracies. Based on the early COVID-19 data in Wuhan, this study estimated that the median time of the early COVID-19 cases from illness onset to local authorities' responses could be reduced to 7.0-10.0 days. Conclusions: This study offers a new solution to transfer traditional medical knowledge into structured data and form diagnosis rules, enables the representation of doctors' logistic thinking and the knowledge transmission among different users. The results of empirical studies demonstrate that by constantly inputting medical knowledge into the system, the proposed method will be capable to detect unknown diseases from existing ones and perform an early response to the initial outbreaks.

Identification of Potential Biomarkers From Hepatocellular Carcinoma With MT1 Deletion.

Background: Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. Metallothioneins (MTs) are metal-binding proteins involved in multiple biological processes such as metal homeostasis and detoxification, as well as in oncogenesis. Copy number variation (CNV) plays a vital role in pathogenesis and carcinogenesis. Nevertheless, there is no study on the role of MT1 CNV in HCC. Methods: Array-based Comparative Genomic Hybridization (aCGH) analysis was performed to obtain the CNV data of 79 Guangxi HCC patients. The prognostic effect of MT1-deletion was analyzed by univariate and multivariate Cox regression analysis. The differentially expressed genes (DEGs) were screened based on The Gene Expression Omnibus database (GEO) and the Liver Hepatocellular Carcinoma of The Cancer Genome Atlas (TCGA-LIHC). Then function and pathway enrichment analysis, protein-protein interaction (PPI) and hub gene selection were applied on the DEGs. Lastly, the hub genes were validated by immunohistochemistry, tissue expression and prognostic analysis. Results: The MT1-deletion was demonstrated to affect the prognosis of HCC and can act as an independent prognostic factor. 147 common DEGs were screened. The most significant cluster of DEGs identified by Molecular Complex Detection (MCODE) indicated that the expression of four MT1s were down-regulated. MT1X and other five hub genes (TTK, BUB1, CYP3A4, NR1I2, CYP8B1) were associated with the prognosis of HCC. TTK, could affect the prognosis of HCC with MT1-deletion and non-deletion. NR1I2, CYP8B1, and BUB1 were associated with the prognosis of HCC with MT1-deletion. Conclusions: In the current study, we demonstrated that MT1-deletion can be an independent prognostic factor in HCC. We identified TTK, BUB1, NR1I2, CYP8B1 by processing microarray data, for the first time revealed the underlying function of MT1 deletion in HCC, MT1-deletion may influence the gene expression in HCC, which may be the potential biomarkers for HCC with MT1 deletion.

Correlating genomic copy number alterations with clinicopathologic findings in 75 cases of hepatocellular carcinoma.

BACKGROUND: Oligonucleotide array comparative genomic hybridization (aCGH) analysis has been used for detecting somatic copy number alterations (CNAs) in various types of tumors. This study aimed to assess the clinical utility of aCGH for cases of hepatocellular carcinoma (HCC) and to evaluate the correlation between CNAs and clinicopathologic findings. METHODS: aCGH was performed on 75 HCC cases with paired DNA samples from tumor and adjacent nontumor tissues. Survival outcomes from these cases were analyzed based on Barcelona-Clinic Liver Cancer Stage (BCLC), Edmondson-Steiner grade (E-S), and recurrence status. Correlation of CNAs with clinicopathologic findings was analyzed by Wilcoxon rank test and clustering vs. K means. RESULTS: The survival outcomes indicated that BCLC stages and recurrence status could be predictors and E-S grades could be a modifier for HCC. The most common CNAs involved gains of 1q and 8q and a loss of 16q (50%), losses of 4q and 17p and a gain of 5p (40%), and losses of 8p and 13q (30%). Analyses of genomic profiles and clusters identified that losses of 4q13.2q35.2 and 10q22.3q26.13 seen in cases of stage A, grade III and nonrecurrence were likely correlated with good survival, while loss of 1p36.31p22.1 and gains of 2q11.2q21.2 and 20p13p11.1 seen in cases of stage C, grade III and recurrence were possibly correlated with worst prognosis. CONCLUSIONS: These results indicated that aCGH analysis could be used to detect recurrent CNAs and involved key genes and pathways in patients with HCC. Further analysis on a large case series to validate the correlation of CNAs with clinicopathologic findings of HCC could provide information to interpret CNAs and predict prognosis.

Prognostic alternative splicing signature in cervical squamous cell carcinoma.

Basing on alternative splicing events (ASEs) databases, the authors herein aim to explore potential prognostic biomarkers for cervical squamous cell carcinoma (CESC). mRNA expression profiles and relevant clinical data of 223 patients with CESC were obtained from The Cancer Genome Atlas (TCGA). Correlated genes, ASEs and percent-splice-in (PSI) were downloaded from SpliceSeq, respectively. The PSI values of survival-associated alternative splicing events (SASEs) were used to construct the basis of a prognostic index (PI). A protein-protein interaction (PPI) network of genes related to SASEs was generated by STRING and analysed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Consequently, 41,776 ASEs were discovered in 19,724 genes, 2596 of which linked with 3669 SASEs. The PPI network of SASEs related genes revealed that TP53 and UBA52 were core genes. The low-risk group had a longer survival period than high-risk counterparts, both groups being defined according to PI constructed upon the top 20 splicing events or PI on the overall splicing events. The AUC value of ROC reached up to 0.88, demonstrating the prognostic potential of PI in CESC. These findings suggested that ASEs involve in the pathogenesis of CESC and may serve as promising prognostic biomarkers for this female malignancy.

[Gene diagnosis and CAG repeat analysis of spinocerebellar ataxia cases of Guangxi region].

To characterize the distributions and subtypes of the spinocerebellar ataxias (SCA) in Guangxi region, the SCAl, SCA2, SCA3/MJD, SCA6, SCA7 and SCA12 (CAG)n mutations were analyzed by polymerase chain reaction (PCR) and capillary electrophoresis (CE). The SCA3/MJD mutation was detected in a total of 21 SCA patients and 19 presymptomatic individuals from 6 SCA families and their CAG repeat numbers were 59-70 and 60-73, respectively. No (CAG)n mutations of SCA1, SCA2, SCA6, SCA7 and SCA12 were detected. This study showed that SCA in Guangxi region is mostly SCA3/MJD subtype and the CAG repeats are smaller than those reported in other regions previously.