BACKGROUND:Cancer stem cel s have self-renewal ability and can differentiate into new tumors. Cancer stem cel s are the source of tumor formation and recurrence, and they can make tumors insensitive to radiotherapy and chemotherapy.
OBJECTIVE:To explore the effect of paclitaxel plus cisplatin on the proliferation and apoptosis of nasopharyngeal cancer stem cel s (NPCSCs) and involved signal pathways.
METHODS:NPCSCs were sorted by immunomagneticbeads and were treated with paclitaxel, cisplatin or their combination. The expression of caspase-3, activated caspase-3 and Bcl-2, which are related to apoptosis, was determined by western blot. The expression ofβ-catenin and its downstream proto-oncogene, c-myc, was also determined by western blot. The activity of the Wnt/β-catenin pathway was inhibited by knocking downβ-catenin expression orβ-catenin inhibitor XAV939. Proliferation and apoptosis of NPCSCs were detected by MTT and flow cytometry, respectively.
RESULTS AND CONCLUSION:Either paclitaxel or cisplatin could inhibit proliferation and induce apoptosis of NPCSCs. The expression of apoptosis marker, activated caspase-3, was increased and the expression of the inhibitor of apoptosis, Bcl-2, was declined. Combined use of paclitaxel and cisplatin had synergistic effect when used together. Either paclitaxel or cisplatin could inhibit the expression ofβ-catenin and c-myc, suppressed the proliferation and induced the apoptosis of NPCSCs by inhibiting the activity of Wnt/β-catenin pathway. These results indicate that the combined use of paclitaxel and cisplatin may inhibit the proliferation of NPCSCs and promote apoptosis via the Wnt/β-catenin pathway.

OBJECTIVETo determine the relationship between the serum sulfur dioxide, homocysteine and the pulmonary arterial pressure in children with congenital heart defects who generated a pulmonary arterial hypertension syndrome (PAH-CHD), and analyze their role in the pathological process of the disease.

METHODThis was a prospective cohort study, children with systemic pulmonary shunt CHD were selected. The patients were divided into three groups: the CHD with no PAH group:n = 20, 10 males, 10 females, 5 with ventricular septal defect (VSD), 8 with atrial septal defect (ASD) and 7 with patent ductus arteriosus (PDA), mean age (1.9 ± 1.8) years; the CHD with mild PAH group:n = 20, 10 males, 10 females, 12 with VSD, 6 with ASD, and 2 with PDA, mean age (1.0 ± 0.8) year; the CHD with moderate or severe PAH group:n = 20, 8 males, 12 females, 12 with VSD, 6 with ASD, and 1 with PDA, 1 with ASD+VSD, mean age (1.8 ± 1.6) year. Twenty healthy children were enrolled from outpatient department as the control group [included 8 males, 12 females, mean age (1.9 ± 1.5) years]. The homocysteine and SO2 concentrations in the serum samples were detected by a modified high performance liquid chromatographic method with fluorescence detection (HPLC-FD), then, multiple comparisons among the groups were performed with analysis of variance, and the pearson correlation.

RESULTThe serum homocysteine concentrations were respectively (11.0 ± 2.7) , (11.7 ± 2.5), (12.0 ± 2.1), (14.3 ± 3.2) µmol/L in the control group, CHD with no PAH group, CHD with mild PAH group, and CHD with moderate or severe PAH group. According to the multiple comparisons, the CHD with moderate or severe PAH group had the highest level (P all < 0.05) .While the comparison within the control group, CHD with none PAH group, and CHD with mild PAH group, the differences were not significant (P all > 0.05). The serum sulfur dioxide strength (concentrated as SO3(2-)) were respectively (10.6 ± 2.4), (8.9 ± 2.3), (7.3 ± 2.9), (4.3 ± 2.1) µmol/L in the control group, CHD with none PAH group, CHD with mild PAH group, and CHD with moderate or severe PAH group. CHD with moderate or severe PAH group had the highest level of serum sulfur dioxide (P < 0.05) . The pearson correlation analysis indicated that in the CHD children, the serum homocysteine were positively correlated with the pulmonary arterial pressure (r = 0.481, P < 0.01), while, the sulfur dioxide were negatively correlated with pulmonary arterial pressure (r = -0.553, P < 0.01).In all children, the serum homocysteine levels were negatively correlated with the sulfur dioxide (r = -0.231, P = 0.039).

CONCLUSIONThe PAH-CHD children had higher homocysteine levels and lower sulfur dioxide levelsl, which demonstrated the disturbance of homocysteine-sulfur dioxide pathway in the sulfur containing amino acids metabolish in the disease. The homocysteine may become a biological marker which reflecting the severities of the PAH-CHD, while the sulfur dioxide can be a new target for the therapy of PAH-CHD.

Biomarkers ; blood ; Case-Control Studies ; Child, Preschool ; Ductus Arteriosus, Patent ; blood ; complications ; physiopathology ; Familial Primary Pulmonary Hypertension ; blood ; etiology ; physiopathology ; Female ; Heart Defects, Congenital ; blood ; complications ; physiopathology ; Heart Septal Defects ; blood ; complications ; physiopathology ; Hemodynamics ; Homocysteine ; blood ; Humans ; Infant ; Male ; Sulfur Dioxide ; blood

Objective:To explore the genetic basis for a child featuring global developmental delay and epilepsy.Methods:A child who had presented at Guangzhou Women and Children′s Medical Center Liuzhou Hospital on February 19, 2023 was selected as the study subject. Clinical data of the child was collected. The child was subjected to whole exome sequencing, and candidate variant was validated by Sanger sequencing and bioinformatic analysis.Results:The child, an 8-month-old girl, had manifested with global developmental delay, epilepsy, and hyperlactacidemia. Cranial MRI revealed diverse hypomyelinating leukodystrophies. Electroencephalogram showed slow background activities. Genetic testing revealed that she has harbored a homozygous variant of the SLC25A12 gene, namely c. 115T>G (p.Phe39Val), for which both of her parents were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be of uncertain significance (PM2_Supporting+ PM3_Supporting+ PP3_Moderate+ PP4_Moderate). I-Mutant v3.0 software predicted that the variant may affect the stability of protein product. Conclusion:The homozygous c. 115T>G (p.Phe39Val) variant of the SLC25A12 gene probably underlay the pathogenesis of the disease in this child.