Bronchial embolisation for infected pulmonary artery pseudoaneurysms causing haemoptysis.

AIM: To report the authors' experience of bronchial artery embolisation (BAE) in a series of patients to control haemoptysis associated with infected pulmonary artery pseudoaneurysms (PAPs). MATERIALS AND METHODS: All patients who underwent BAE based on computed tomography angiography (CTA) findings indicative of haemoptysis between February 2019 and September 2022 at Xiangyang Central Hospital were identified. Charts of patients with haemoptysis and infectious PAPs were reviewed retrospectively. Data were collected data on age, sex, underlying pathology, source pulmonary artery of the PAP, association with cavitary lesions or consolidation, systemic angiography findings, technical and clinical success, and follow-up. RESULTS: Seventeen PAPs were treated in 16 patients, with a mean age of 60.3 years (range: 37-82 years). The most common underlying cause was tuberculosis (15/16, 93.8%). Imaging by CTA did not identify the source pulmonary artery for 15 (88.2%) PAPs; all were associated with cavitary lesions or consolidation. All PAPs were visualised on systemic angiography. The technical and clinical success rates were both 87.5%. Two patients who experienced a recurrence of haemoptysis during follow-up underwent repeat CTA, which confirmed the elimination of the previous PAP. CONCLUSION: BAE may be a valuable technique to control haemoptysis associated with infectious PAPs that are visualised on systemic angiography. A possible contributing factor is PAPs arising from very small pulmonary arteries.

TFP5, a Peptide Derived from Cdk5 Activator p35, Protects Pancreatic ß Cells from Glucose Toxicity.

We studied the effect of TFP5 on MIN6 cells (cultured mouse islet ß cells) treated with different concentrations of glucose (5 or 25 mM). The results were verified in C57BL/6J mice (control; n=12) and db/db mice with type 2 diabetes mellitus (n=12). To synthesize TFP5, peptide p5 (a derivative of p35 protein, activator of cyclin-dependent kinase 5, Cdk5) was conjugated with a FITC tag at the N-terminus and an 11-amino acid TAT protein transduction domain at the C-terminus. TFP5 was employed to inhibit Cdk5 activity and then to evaluate its efficiency in treating experimental type 2 diabetes mellitus. TFP5 effectively inhibited the pathological hyperactivity of Cdk5, enhanced insulin secretion, and protected pancreatic ß cells from apoptosis in vitro and in vivo. In addition, TFP5 inhibited inflammation in pancreatic islets by reducing the expression of inflammatory cytokines TGF-ß1, TNFα, and IL-1ß. These novel data indicates that TFP5 is a promising candidate for treatment of type 2 diabetes mellitus.

IGHG1 functions as an oncogene in tongue squamous cell carcinoma via JAK1/STAT5 signaling.

The article "IGHG1 functions as an oncogene in tongue squamous cell carcinoma via JAK1/STAT5 signaling, by Y.-L. Zheng, Y.-Y. Li, J.-F. Xie, H.-Q. Ma, published in Eur Rev Med Pharmacol Sci 2020; 24 (12): 6716-6725-DOI: 10.26355/eurrev_202006_21659-PMID: 32633362" has been withdrawn from the authors stating that "the experimental data in the article are wrong". The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21659.

IGHG1 functions as an oncogene in tongue squamous cell carcinoma via JAK1/STAT5 signaling.

OBJECTIVE: We explored the IgG1 heavy chain constant region (IGHG1) roles in tongue squamous cell carcinoma (TSCC) progression, as well as to probe the underlying mechanisms. PATIENTS AND METHODS: The expression patterns of IGHG1 in TSCC tissues and cell lines were tested by Western blotting, quantitative real-time PCR (RT-PCR) and immunohistochemistry (IHC) technologies. The relationship between IGHG1 expression level and the overall survival and clinicopathologic features of patients with TSCC were evaluated to assess the clinical value of IGHG1. The effects of IGHG1 on cell function were determined by Cell-Counting Kit-8 (CCK-8), clone formation, flow cytometry and in vivo tumor formation assays. RESULTS: The expression of IGHG1 in TSCC tissues and cell lines was significantly elevated at both mRNA and protein levels. IGHG1 expression levels closely related to T classification (p=0.008), clinical stage (p=0.011), and node metastasis (p=0.005) in TSCC patients. Upregulation of IGHG1 with lentivirus infection significantly increased Janus kinase 1 (JAK1) expression and the phosphorylation level of signal transducer and activator of transcription 5 (STAT5). In addition, IGHG1 overexpression markedly enhanced cell proliferation, clone formation and tumorigenesis and inhibited cell apoptosis, whereas these effects were abolished when JAK1 was downregulated in SCC15 and SCC4 TSCC cell lines. CONCLUSIONS: Collectively, this study reveals that IGHG1 functions as an oncogene in TSCC via activating JAK1/STAT5 signaling.

Hypoxia promotes invasion of retinoblastoma cells in vitro by upregulating HIF-1α/MMP9 signaling pathway.

OBJECTIVE: The aim of this study is to investigate the effect of hypoxia-inducible transcription factors-1α (HIF-1α)/matrix metalloproteinase 9 (MMP9) signaling pathway on hypoxia triggered invasion in retinoblastoma cell line HXO-RB44. MATERIALS AND METHODS: HXO-RB44 cells were cultured under hypoxia conditions for 24 h. The effect of hypoxia on invasion ability of HXO-RB44 cells was monitored with transwell invasion assay; the mRNA and protein expression levels of HIF-1α and MMP9 were detected by Real-time polymerase chain reaction (RT-PCR) and Western blot; luciferase assay was performed to assess the MMP9 regulation by HIF-1α, and HIF-1α regulation by hypoxia. Furthermore, HIF-1α and MMP9 siRNA were used to investigate the effect of HIF-1α/MMP9 signaling on hypoxia-induced cell invasion. RESULTS: The results demonstrated that hypoxia could promote HXO-RB44 cells invasion. The mRNA and protein level of HIF-1α and MMP9 were upregulated by hypoxia treatment, whereas HIF-1α and MMP9 siRNA could reverse these processes. CONCLUSIONS: Hypoxia promotes retinoblastoma cell line HXO-RB44 invasion by activating HIF-1α/MMP9 signaling pathway.

An extracellular matrix culture system for induced pluripotent stem cells derived from human dental pulp cells.

OBJECTIVE: Induced pluripotent stem cells (iPSCs) have emerged as a promising tool for treating incurable diseases. The current challenges are to avoid potential xenopathogenic transmission and immune rejection potentially caused by exposure of iPSCs to animal-derived products. In addition, an efficient feeder cell-free culture condition will be required for minimizing batch-to-batch variation and facilitating scale-up. Therefore, establishing an efficient extracellular matrix (ECM) culture system is considered as a prerequisite for the future clinical application of iPSC-based cell therapies. In this study, we evaluated the feasibility of culturing iPSCs in ECM derived from human dental pulp cells (hDCP). MATERIALS AND METHODS: iPSCs growing in Matrigel were transferred to ECM or Matrigel and cultured in mTeSRTM1 medium. RESULTS: The number of adherent cells in the ECM group was higher than that in the Matrigel group after incubation for 8, 12, and 24 h, indicating that the ECM could enhance cell adherence. The adhesion of cells to ECM not only depends on simple physical attachment with ECM, but also mediated by fibronectin in the ECM. The hDPC-iPSCs showed orderly growth in the ECM, suggesting that the ECM could promote the growth and proliferation of hDPC-iPSCs. We also observed that stem cells growed along to avoid contact inhibition. CONCLUSIONS: The iPSCs maintained undifferentiated state when cultured in ECM when the iPSCs and ECM are of the same cell origin. ECM and mTeSRTM1, can both be used as new culture medium for iPSCs that facilitates the clinical application of iPSC-based cell therapies in the future.

Acute and chronic stress differentially regulate cyclin-dependent kinase 5 in mouse brain: implications to glucocorticoid actions and major depression.

Stress activates the hypothalamic-pituitary-adrenal axis, which in turn increases circulating glucocorticoid concentrations and stimulates the glucocorticoid receptor (GR). Chronically elevated glucocorticoids by repetitive exposure to stress are implicated in major depression and anxiety disorders. Cyclin-dependent kinase 5 (CDK5), a molecule essential for nervous system development, function and pathogenesis of neurodegenerative disorders, can modulate GR activity through phosphorylation. We examined potential contribution of CDK5 to stress response and pathophysiology of major depression. In mice, acute immobilized stress (AS) caused a biphasic effect on CDK5 activity, initially reducing but increasing afterwards in prefrontal cortex (PFC) and hippocampus (HIPPO), whereas chronic unpredictable stress (CS) strongly increased it in these brain areas, indicating that AS and CS differentially regulate this kinase activity in a brain region-specific fashion. GR phosphorylation contemporaneously followed the observed changes of CDK5 activity after AS, thus CDK5 may in part alter GR phosphorylation upon this stress. In the postmortem brains of subjects with major depression, CDK5 activity was elevated in Brodmann's area 25, but not in entire PFC and HIPPO. Messenger RNA expression of glucocorticoid-regulated/stress-related genes showed distinct expression profiles in several brain areas of these stressed mice or depressive subjects in which CDK5-mediated changes in GR phosphorylation may have some regulatory roles. Taken together, these results indicate that CDK5 is an integral component of stress response and major depression with regulatory means specific to different stressors, brain areas and diseases in part through changing phosphorylation of GR.

Association between the c.910A>G genetic variant of the XRCC1 gene and susceptibility to esophageal cancer in the Chinese Han population

Esophageal cancer (EC) is a common malignancy worldwide. The X-ray repair cross-complementing 1 gene (XRCC1) is one of the most important candidate genes for influencing susceptibility to EC. This study aimed to investigate the effect of XRCC1 genetic variants on susceptibility to EC. A total of 383 EC patients (males: 239, females: 144, mean age: 56.62) and 387 cancer-free controls (males: 251, females: 136, mean age: 58.23) were enrolled in this study. The c.910A>G genetic variant of the XRCC1 gene was determined by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods. The allele and genotype frequencies indicated statistical differences between EC patients and cancer-free controls. The c.910A>G genetic variant was statistically associated with increased susceptibility to EC [GG vs AA: odds ratio (OR)=1.79, 95% confidence interval (CI)=1.12-2.86, P=0.014; GG vs AG/AA: OR=1.76, 95%CI=1.13-2.75, P=0.013; G vs A: OR=1.25, 95%CI=1.01-1.55, P=0.041]. The allele G and genotype GG could contribute to the increased susceptibility to EC. Our findings suggest that the c.910A>G genetic variant is associated with susceptibility to EC in the Chinese Han population, and might be used as a molecular marker for detecting susceptibility to EC.

Major QTL for Fusarium crown rot resistance in a barley landrace.

Fusarium crown rot (FCR) is a serious cereal disease in semi-arid regions worldwide. In assisting the effort of breeding cultivars with enhanced resistance, we identified several barley genotypes with high levels of FCR resistance. One of these genotypes, AWCS079 which is a barley landrace originating from Japan, was investigated by developing and assessing three populations of recombinant inbred lines. Two QTL, one located on the long arm of chromosome 1H (designated as Qcrs.cpi-1H) and the other on 3HL (designated as Qcrs.cpi-3H), were found to be responsible for the FCR resistance of this genotype. Qcrs.cpi-1H is novel as no other FCR loci have been reported on this chromosome arm. Qcrs.cpi-3H co-located with a reduced height (Rht) locus and the effectiveness of the former was significantly affected by the latter. The total phenotypic variance explained by these two QTL was over 60 %. Significant effects were detected for each of the QTL in each of the three populations assessed. The existence of these loci with major effects should not only facilitate breeding and exploitation of FCR-resistant barley cultivars but also their further characterization based on fine mapping and map-based gene cloning.

Haploidentical allogeneic haematopoietic stem cell transplantation as salvage therapy for engraftment failure after unrelated and autologous stem cell transplantation: a case report and review of the literature.

Engraftment failure is a rare but life-threatening complication of haematopoietic stem cell transplantation (HSCT) and treatment of this condition is often challenging. This case report describes a patient with acute myeloid leukaemia and engraftment failure after unrelated donor allogeneic stem cell transplantation. Rescue treatment with granulocyte-colony stimulating factor and reinfusion of autologous 'back-up' stem cells failed, but transplantation of haploidentical donor stem cells following a fludarabine and antithymocyte globulin (ATG)-based conditioning regimen resulted in haematological reconstitution and long-term disease-free survival. The use of haploidentical donor stem cell transplantation as salvage therapy after engraftment failure in adult patients has not, to the authors' knowledge, been previously reported. Additionally, a review of the relevant literature is presented. This case report and literature review suggest that reinfusion of cryopreserved 'back-up' haematopoietic stem cells is a safe and effective salvage therapy for engraftment failure after allogeneic HSCT. Haploidentical donor stem cell transplantation after a fludarabine and ATG-based conditioning regimen could provide effective second-line therapy in adult patients.

Characterization of ω-secalin genes from rye, triticale, and a wheat 1BL/1RS translocation line.

Sixty-two DNA sequences for the coding regions of omega-secalin (ω-secalin) genes have been characterized from rye (Secale cereale L.), hexaploid and octoploid triticale (× Triticosecale Wittmack), and wheat (Triticum aestivum L.) 1BL/1RS translocation line. Only 19 out of the 62 ω-secalin gene sequences were full-length open reading frames (ORFs), which can be expressed into functional proteins. The other 43 DNA sequences were pseudogenes, as their ORFs were interrupted by one or a few stop codons or frameshift mutations. The 19 ω-secalin genes have a typical primary structure, which is different from wheat gliadins. There was no cysteine residue in ω-secalin proteins, and the potential celiac disease (CD) toxic epitope (PQQP) was identified to appear frequently in the repetitive domains. The ω-secalin genes from various cereal species shared high homology in their gene sequences. The ω-secalin gene family has involved fewer variations after the integration of the rye R chromosome or whole genome into the wheat or triticale genome. The higher Ka/Ks ratio (i.e. non-synonymous to synonymous substitutions per site) in ω-secalin pseudogenes than in ω-secalin ORFs indicate that the pseudogenes may be subject to a reduced selection pressure. Based on the conserved sequences of ω-secalin genes, it will be possible to manipulate the expression of this gene family in rye, triticale, or wheat 1BL/1RS translocation lines, to reduce its negative effects on grain quality.

Molecular characterization of novel low-molecular-weight glutenin genes in Aegilops longissima.

Extensive genetic variations of low-molecular-weight glutenin subunits (LMW-GS) and their coding genes were found in the wild diploid A- and D-genome donors of common wheat. In this study, we reported the isolation and characterization of 8 novel LMW-GS genes from Ae.longissima Schweinf. & Muschl., a species of the section Sitopsis of the genus Aegilops, which is closely related to the B genome of common wheat. Based on the N-terminal domain sequences, the 8 genes were divided into 3 groups. A consensus alignment of the extremely conserved domains with known gene groups and the subsequent cluster analysis showed that 2 out of the 3 groups of LMW-GS genes were closely related to those from the B genome, and the remaining was related to those from A and D genomes of wheat and Ae. tauschii. Using 3 sets of gene-group-specific primers, PCRs in diploid, tetraploid and hexaploid wheats and Ae. tauschii failed to obtain the expected products, indicating that the 3 groups of LMW-GS genes obtained in this study were new members of LMW-GS multi-gene families. These results suggested that the Sitopsis species of the genus Aegilops with novel gene variations could be used as valuable gene resources of LMW-GS. The 3 sets of group-specific primers could be utilized as molecular markers to investigate the introgression of novel alien LMW-GS genes from Ae. longissima into wheat.

Length variations of i-type low-molecular-weight glutenin subunit genes in diploid wheats.

Allelic variation of the low-molecular-weight glutenin subunit (LMW-GS) is associated with the significant differences of dough quality in bread and durum wheat, and has been widely evaluated at protein level in wheat and its relatives. In this study, a PCR primer set, targeting the high variable repetitive domains, was employed to assay the length variation of i-type LMW-GS genes in the A-genomes of diploid wheats, the diploid progenitors of tetraploid and hexaploid wheat. A total of 71 accessions of diploid wheats, belonging to two wild and one cultivated species, were investigated. The higher variations of repetitive length in i-type LMW-GS genes were found in diploid wheats with Nei's genetic variation index (H) of 0.834. The two wild species, T. boeoticum and T. urartu, were found to possess the similar degree of variability, with the Nei's genetic variation index of 0.806 and 0.783, respectively. Less variations were detected in T. monococcum (H = 0.680), a cultivated species domesticated from T. boeoticum. The sufficient variations found in this study could be used as valuable sources for the enrichment of the genetic variations and the alteration of flour-processing properties of the cultivated wheat. To our knowledge, it was the first time that an analysis of length variation targeting a particular group of genes of LMW-GS complex multigene families was conducted.

Characterization of one newly established esophageal cancer cell line CSEC from a high-incidence area in China.

The Chaoshan littoral is located in a high-incidence area of esophageal cancer in the south of China. In this study, a new esophageal cancer cell line CSEC was established from a 47-year-old female Chinese patient in this district. The biological characters of the cultured cells were investigated, including morphology, ultrastructure, growth kinetic features, tumorigenicity, expression of tumor-associated antigen and cytogenetic features. CSEC cell line grew continuously with a doubling time of 39.5 h and had been passaged over 80 times. The CSEC cells possessed features of squamous epithelial cells with cytokeratin indicated by immunohistochemical staining and tonofilaments and desmosomes revealed by electron microscopy. Tumorigenicity to severe combined immunodeficient mice was confirmed and the tumors developed revealed well-differentiated squamous cell carcinoma, similar to the origin tumor from which the cell line derived. The cytogenetic analysis demonstrated hypertetraploid karyotypes. Chromosome structure aberrations were common and complicated. Immunohistochemical staining showed that CSEC cells were infected with HPV and over-expressed p53. In summary, the CSEC cell line is a well-differentiated esophageal squamous cell carcinoma cell line from a high-incidence area in southern China. It may provide a useful model for the pathogenesis and therapeutic research of esophageal squamous cell carcinoma.

Correlation between enhancement pattern of hepatocellular carcinoma on real-time contrast-enhanced ultrasound and tumour cellular differentiation on histopathology.

The objective of this study was to evaluate the correlation between the enhancement pattern of hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS) and tumour cellular differentiation on histopathology. 189 HCC lesions in 189 patients were retrospectively evaluated with CEUS and histopathological examination. CEUS was performed with SonoVue and contrast pulse sequencing. Histopathological diagnoses were made according to the Edmonson grading system. Significant differences were shown between the time that the HCC became hypoenhancing or remained echogenic in late phase and tumour cellular differentiation (p = 0.006; p = 0.036), but not with the time of commencement of hyperenhancing or commencement of isoenhancing in arterial phase and portal phase (p = 0.164, p = 0.113; p = 0.186, p = 0.070). The timing of HCC becoming hypoenhancing on CEUS is correlated with tumour cellular differentiation; well differentiated tumours wash out more slowly than poorly differentiated ones.

Percutaneous thermal ablation for recurrent hepatocellular carcinoma after hepatectomy.

BACKGROUND: Tumour ablation using a thermal energy source has shown promising results, and is particularly suitable for recurrent hepatocellular carcinoma (HCC). The present study evaluated long-term outcomes after percutaneous thermal ablation for recurrent HCC following liver resection. METHODS: Radiofrequency ablation or microwave ablation was used to treat a total of 124 tumour nodules (0.9-7.0 cm in diameter) in 72 patients with recurrent HCC. RESULTS: Complete ablation of 119 (96.0 per cent) of 124 tumour nodules was achieved. There was no treatment-related death and the major complication rate was 4 per cent. During a mean(s.d.) follow-up of 27.9(17.8) months, local recurrence developed in 16 (13.6 per cent) of 118 successfully treated tumour nodules. Distant recurrence developed in 60 (85 per cent) of 71 patients, of whom 26 had repeat metachronous distant recurrence. With repeated ablation for both local and distant recurrence, the 1-, 3- and 5-year overall survival rates after initial ablation were 75, 43 and 18 per cent respectively. Patients with a serum alpha-fetoprotein level greater than 200 ng/ml before treatment had significantly poorer survival than those with a lower level (P = 0.034) and multivariate analysis identified preablation AFP level as an independent prognostic factor (P = 0.054). CONCLUSION: With their advantages of preservation of non-tumorous liver tissue and easy repetition, percutaneous thermal ablative therapies were particularly suitable for recurrent HCC and improved long-term survival.