Generation of an induced pluripotent stem cell line from a type 1 neurofibromatosis patient with NF1 mutation.

A human induced pluripotent stem cell (iPSC) line was generated from patient with type 1 neurofibromatosis (NF-1), carrying heterozygous mutation in NF1 gene. Peripheral blood mononuclear cells (PBMCs) were reprogrammed using non-integrating delivery of KFL4, OCT4, SOX2, BCL-XL and c-MYC. The iPSC line expresses pluripotency markers, displays a normal karyotype, and is able to differentiate into three germ layers in vitro. This iPSC line represents a valuable cell model for NF1 in humans.

REC8 regulates neuroblastoma cell proliferation, migration, invasion, and angiogenesis via STAT3/VEGF signaling.

BACKGROUND: Neuroblastoma, one of the most prevalent childhood cancers, is often treated with surgery, radiation, and chemotherapy. However, prognosis and survival are still dismal for children with neuroblastoma at high risk. Consequently, it is vital to identify new and effective treatment targets. As a component of the meiotic cohesion complex, REC8 is involved in a wide range of malignancies. The current work assessed the impact of REC8 knockdown on SH-SY5Y and SK-N-AS neuroblastoma cells and delved into the molecular mechanism behind this effect. METHODS: Knockdown of REC8 using the small interfering (si) RNA technology, and the results were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot. The Cell Counting Kit-8 (CCK-8) was used to examine cell proliferation, while flow cytometry was used to examine cell cycle progression and apoptosis. Analyses of angiogenesis included tube formation experiments. Transwell tests were used to examine cell migration and invasion. RESULTS: The data showed that downregulation of the REC8 led to a substantial decrease in cell proliferation by stopping the cell cycle in the G1 phase. REC8 knockdown significantly reduced neuroblastoma cell proliferation, migration, invasion, angiogenesis, induced cell cycle arrest, and enhanced apoptosis. We also discovered that repressing REC8 expression in neuroblastoma cell lines SH-SY5Y and SK-N-AS reduced their ability to activate the STAT3/VEGF signaling pathway. CONCLUSIONS: Neuroblastoma therapy may benefit from targeting REC8 and its downstream targets.

Comparative analysis of the lung microbiota in patients with respiratory infections, tuberculosis, and lung cancer: A preliminary study.

Recent evidence suggests that lung microbiota can be recognized as one of the ecological determinants of various respiratory diseases. However, alterations in the lung microbiota and associated lung immunity in these respiratory diseases remain unclear. To compare the lung microbiota and lung immune profiles in common respiratory diseases, a total of 78 patients were enrolled in the present study, including 21 patients with primary pulmonary tuberculosis (PTB), eight patients with newly diagnosed lung cancer (LC), and 49 patients with community-acquired pneumonia (CAP). Bronchoalveolar lavage fluid (BALF) was collected for microbiota and cytokine analyses. With MiSeq sequencing system, increased bacterial alpha-diversity and richness were observed in patients with LC than in those with PTB and CAP. Linear discriminant analysis effect size revealed that CAP-associated pulmonary microbiota were significantly different between the PTB and LC groups. More key functionally different genera were found in the PTB and LC groups than in the CAP group. The interaction network revealed stronger positive and negative correlations among these genera in the LC group than in the other two groups. However, increased BALF cytokine profiles were observed in the PTB group than in the other two groups, while BALF cytokines were correlated with key functional bacteria. This comparative study provides evidence for the associations among altered lung microbiota, BALF inflammation, and different respiratory disorders, which provides insight into the possible roles and mechanisms of pulmonary microbiota in the progression of respiratory disorders.

Identification of a novel mutation in CYBB gene in a Chinese neonate with X-linked chronic granulomatous disease: A case report.

RATIONALE: X-linked chronic granulomatous disease (X-CGD) is an X-linked recessive disorder of the Nicotinamide adenine dinucleotide phosphate oxidase system that can cause primary immunodeficiency. Mutations in the CYBB gene located in Xp21.1 were accounting for X-CGD disease. More than 600 mutations have been identified as the cause of X-CGD in various populations worldwide. PATIENT CONCERNS AND DIAGNOSIS: In this study, the proband suffered from elevated white blood cells (WBC, 23.65 × 109/L), mainly in neutral (16.4 × 109/L). The neutrophil oxidative index of the patient was 2.13, which was extremely low, whereas his mother was 69.0 (Ref >100). Next, next-generation sequencing of the primary immunodeficiency diseases -related gene panel was performed. One novel mutation was identified in the CYBB gene in the CGD case: c.55C>G in exon 2. The mutation was verified by Sanger sequencing. The mother of the patient was heterozygous for the c.55C>G mutation, and the father was normal. These mutations were not present in the 100 unrelated normal controls. INTERVENTIONS AND OUTCOMES: The patient died from severe and uncontrollable pulmonary infection at 3 months of age. LESSONS: The identification of these mutations in this study further expands the spectrum of known CYBB gene mutations and contributes to the genetic counseling and prenatal molecular diagnosis of X-CGD.

Identification of a novel missense mutation in the TPM1 gene via exome sequencing in a Chinese family with dilated cardiomyopathy: A case report and literature review.

RATIONALE: Dilated cardiomyopathy (DCM) is a cardiovascular disorder characterized by consecutive ventricular dilation and contractile dysfunction, often leading to congestive heart failure. DCM type 1Y (DCM1Y) is caused by a mutation in the TPM1 (tropomyosin 1) gene. To date, about thirty TPM1 gene mutations have been reported to be related to DCM1Y. However, mutational screening of the TPM1 gene is still far from being complete. Identification of TPM1 mutation is particularly important in the diagnosis of DCM1Y and will give more insights into the molecular pathogenesis of DCM1Y. PATIENT CONCERNS: A Chinese Han family with DCM phenotypes was examined. DIAGNOSIS: A novel missense mutation, c.340G > C in exon 3 of the TPM1 gene, was identified. INTERVENTIONS: Next-generation sequencing (NGS) of DNA samples was performed to detect the gene mutation in the proband, which was confirmed by Sanger sequencing. OUTCOMES: This novel heterozygous mutation results in the substitution of glutamic acid with glutamine (p.E114Q). Based on this finding and clinical manifestations, a final diagnosis of DCM1Y was made. LESSONS: We present evidence that p.E114Q mutation represents a novel TPM1 mutation in a Chinese Han family with DCM. Our data expand the mutation spectrum of the TPM1 gene and may facilitate the clinical diagnosis of DCM1Y.

Management of duodenal atresia associated with situs inversus abdominus: A case report.

RATIONALE: Duodenal atresia in association with situs inversus abdominus is extremely rare. Care should be taken when selecting appropriate surgical methods, and caution should be exercised during the surgery to avoid misdiagnosis and mistreatment. With prompt recognition of the condition, the surgical procedure should be performed in a timely manner to achieve positive results. PATIENT CONCERNS: A newborn affected by situs inversus abdominus associated with duodenal atresia, midgut malrotation, and volvulus. DIAGNOSIS: Congenital duodenal atresia with situs inversus abdominis. INTERVENTIONS: Diamond-shaped duodenoduodenostomy with appendectomy was performed, with the release of Ladd band and correction of the malrotation. OUTCOMES: The baby boy is thriving well with no abdominal complaints at 4 years of surgical follow-up. LESSONS: Although several theories are put forward to clarify this matter, the proper cause of duodenal atresia is not well defined. Clinical symptoms and examinations can assist diagnosis, the definitive cause should be ascertained by surgical approach. And the operating surgeon must be aware of the "mirror anatomy" to prevent unnecessary injuries. Additionally, long-term prognosis for duodenal atresia are very good, therefore, careful attention in postoperative management are important in such a case.

Dynamic transcriptomes of resistant and susceptible peach lines after infestation by green peach aphids (Myzus persicae Sülzer) reveal defence responses controlled by the Rm3 locus.

BACKGROUND: The green peach aphid (GPA), Myzus persicae (Sülzer), is a widespread phloem-feeding insect that significantly influences the yield and visual quality of peach [Prunus persica (L.) Batsch]. Single dominant gene (Rm3)-based resistance provides effective management of this invasive pest, although little is known about the molecular responses of plants to GPA feeding. RESULTS: To illustrate the molecular mechanisms of monogenic resistance in peach to young tissue-infecting GPAs, aphid-resistant/aphid-susceptible peach lines from a segregating population with Rm3/rm3 and rm3/rm3 genotypes were infested with GPAs for 3 to 72 h. Transcriptome analysis of the infested tissues identified 3854 differentially expressed genes (DEGs). Although the majority of the DEGs in the resistant line also responded to aphid attack in the susceptible line, the overall magnitude of change was greater in the resistant line than in the susceptible line. The enriched gene ontology of the 3854 DEGs involved in plant defence responses included redox situation, calcium-mediated signalling, transcription factor (e.g., WRKY, MYB, and ERF), MAPK signalling cascade, phytohormone signalling, pathogenesis-related protein, and secondary metabolite terms. Of the 53 genes annotated in a 460 kb interval of the rm3 locus, seven genes were differentially expressed between the aphid-resistant and aphid-susceptible peach lines following aphid infestation. CONCLUSIONS: Together, these results suggest that the Rm3-dependent resistance relies mainly on the inducible expression of defence-related pathways and signalling elements within hours after the initiation of aphid feeding and that the production of specific secondary metabolites from phenylpropanoid/flavonoid pathways can have major effects on peach-aphid interactions.