Ku80 cooperates with CBP to promote COX-2 expression and tumor growth.

Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung cancers. We conclude that Ku80 promotes COX-2 expression and tumor growth and is a potential therapeutic target in lung cancer

Plasma mRNA expression levels of BRCA1 and TS as potential predictive biomarkers for chemotherapy in gastric cancer

OBJECTIVE: Personalized chemotherapy based on predictive biomarkers can maximize efficacy. However, tumor tissue obtained at the time of initial diagnosis will not reflect genetic alterations observed at the time of disease progression. We have examined whether plasma mRNA levels can be a surrogate for tumor levels in predicting chemosensitivity. METHODS: In 150 gastric cancer patients, mRNA levels of BRCA1 and TS were assessed in plasma and paired tumor tissue. The Mann-Whitney U-test was used to compare mRNA expression levels between tumor samples exhibiting in vitro sensitivity or resistance to docetaxel and pemetrexed. All statistical tests were two-sided. RESULTS: There were significant correlations between plasma and tumor mRNA levels of BRCA1 (rho = 0.696, P < 0.001) and TS (rho = 0.620, P < 0.001). BRCA1 levels in plasma (docetaxel-sensitive: 1.25; docetaxel-resistant: 0.50, P < 0.001) and tumor (docetaxel-sensitive: 8.81; docetaxel-resistant: 4.88, P < 0.001) were positively associated with docetaxel sensitivity. TS levels in plasma (pemetrexed-sensitive: 0.90; pemetrexed-resistant: 1.82, P < 0.001) and tumor (pemetrexed-sensitive: 6.56; pemetrexed-resistant: 16.69, P < 0.001) were negatively associated with pemetrexed sensitivity. CONCLUSIONS: Plasma mRNA expression levels mirror those in the tumor and may have a promising role as potential predictive biomarkers for chemotherapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-014-0355-2) contains supplementary material, which is available to authorized users

Research Progress on Risk Factors of Preoperative Anxiety in Children: A Scoping Review

Background: Preoperative anxiety has adverse effects on children and negative impacts on postoperative rehabilitation. Anesthesiologists can accurately identify children with preoperative anxiety, and individualized intervention can effectively improve their psychological state and clinical prognosis. However, a comprehensive summary of the current available evidence has yet to be conducted. Searches were conducted in Medline databases from inception to March 2022. Primary studies that reported preoperative anxiety in children and its attendant effects on postoperative recovery and prognosis were screened and included. Among the 309 publications identified, 12 related studies (n = 3540 patients) met the eligibility criteria. The incidence of preoperative anxiety in children in the included studies ranged from 41.7% to 75.44%. While 16 influencing factors were identified, only 5 factors had a significant impact on preoperative anxiety in children: younger age (n = 8), parental anxiety (n = 7), negative previous hospitalizations (n = 3), less sociableness (n = 2), and surgical setting (n = 1). The current scoping review identified risk factors for preoperative anxiety in children. Healthcare workers should identify and manage preoperatively anxious children. There are still some factors that are controversial, and large-scale clinical studies are needed

Development and Characterization of Transcription Factor Gene-Derived Microsatellite (TFGM) Markers in Medicago truncatula and Their Transferability in Leguminous and Non-Leguminous Species

Transcription factors (TFs) are critical adaptor molecules that regulate many plant processes by controlling gene expression. The recent increase in the availability of TF data has made TFs a valuable resource for genic functional microsatellite marker development. In the present study, we developed TF gene-derived microsatellite (TFGM) markers for Medicago truncatula and assessed their cross-species transferability. A total of 203 SSRs were identified from 1467 M. truncatula TF coding sequences, 87.68% of which were trinucleotide repeats, followed by mono- (4.93%) and hexanucleotide repeats (1.48%). Further, 142 TFGM markers showed a high level of transferability to the leguminous (55.63%–85.21%) and non-leguminous (28.17%–50.00%) species. Polymorphisms of 27 TFGM markers were evaluated in 44 alfalfa accessions. The allele number per marker ranged from two to eight with an average of 4.41, and the PIC values ranged from 0.08 to 0.84 with an average of 0.60. Considering the high polymorphism, these TFGM markers developed in our study will be valuable for genetic relationship assessments, marker-assisted selection and comparative genomic studies in leguminous and non-leguminous species

Theoretical Study on the Mechanism of Palladium-Catalyzed Dearomatization Reaction of Chloromethylnaphthalene

The Pd-catalyzed dearomatization of chloromethylnaphthalene with allenyltributylstannane has been investigated at the B3LYP density functional level of theory. The calculations indicate that the monophosphine complex is catalytically more active than the bisphosphine complex for oxidative addition. The transmetalation step is a crucial step for determining the dearomatized products due to the formation of two stable bis-π-complexes. It is found that reductive elimination occurs by coupling the terminal carbons of the η¹-propargyl ligand and η¹-allenyl ligand with the <i>para</i>-carbons of the η³-methylnaphthalene ligands in η³-methylnaphthalene-η¹-propargyl-Pd­(PH₃) and η³-methylnaphthalene-η¹-allenyl-Pd­(PH₃) to form the corresponding allenylated and propargylated dearomatization products. For comparison, various C–C coupling pathways in reductive elimination have also been studied

Preharvest Reduction in Nutrient Solution Supply of Pepper (<i>Capsicum annuum</i> L.) Contributes to Improve Fruit Quality and Fertilizer Efficiency While Stabilising Yields

Optimising fertilisation is an important part of maximising vegetable yield and quality whilst minimising environmental hazards. An accurate and efficient scheme of irrigation and fertiliser based on plants’ nutrient requirements at different growth stages is essential for the effective intensive production of greenhouse pepper (Capsicum annuum L.). In this study, the effects of reducing fertilisation rate by 20%, 40%, 60% and 80% from the day 6 to day 0 before harvest for each layer of peppers on growth, yield, quality and nutrient utilisation were evaluated. The results showed that the morphological indicators (plant height and stem diameter) and biomass of plants decreased gradually with the increase in fertiliser reduction rate. Compared with control (CK) plants, the 20–40% reduction in fertiliser application rate did not cause a significant decrease in biomass and stem diameter but significantly increased the accumulation of N (13.52–15.73%), P (23.09% in 20% reducted-treatment) and K (13.22–14.21%) elements in plants. The 20–80% reduction in fertiliser application before harvest had no significant effects on the nutrient agronomic efficiency of N, P and K elements. However, it decreased the physiological nutrient efficiency and significantly improved the nutrient harvest index of N, P and K. Appropriate reduction in fertiliser application significantly increased the nutrient recovery efficiency (20–40% reduction) and nutrient partial-factor productivity (40% reduction) of N (3.35–6.00% and 12.87%), P (2.47–2.92% and 14.01%) and K (7.49–15.68% and 14.01%), respectively. Furthermore, reducing the fertilisation rate by 20–40% before each harvest had a certain positive effect on the C and N metabolism of pepper leaves and fruits. In particular, the activities of N metabolism-related enzymes (nitrate reductase, nitrite reductase, glutamine synthase, glutamate synthase and glutamate dehydrogenase) and C metabolism-related enzymes (sucrose phosphate synthase, sucrose synthetase, acid invertase and neutral invertase) in leaves and fruits did not significantly different or significantly increased compared with those in CK plants. The results of the representative aromatic substance contents in the fruit screened by the random forest model showed that compared with the CK plants, reducing the fertiliser application by 20–40% before harvest significantly increased the content of capsaicin and main flavour substances in the fruit on the basis of stable yield. In summary, in the process of pepper substrate cultivation, reducing the application of nutrients by 40% from the day 6 to day 0 before each harvest could result in stable yield and quality improvement of the pepper. These results have important implications for institutional precision fertilisation programs and the improvement of the agroecological environment

Synergistic anticancer effects of polyphyllin I and evodiamine on freshly-removed human gastric tumors.

The present study was designed to examine the anticancer effect of Traditional Chinese Medicine of polyphyllin I (PPI) and evodiamine (EVO) on freshly-removed gastric tumor tissues.Sixty freshly-removed gastric tumor tissues were collected. Their sensitivity to PPI, EVO, platinum (Pt), 5-FU, irinotecan (CPT-11) were determined by histoculture drug response assay (HDRA). Those samples were also formalin-fixed and paraffin-embedded, which were used to examine the mRNA expression levels of aprataxin(APTX), excision repair cross-complementing 1(ERCC1), thymidylate synthase(TS) and topoisomerase I(TOPO1) by quantitative RT-PCR. The association of the gene expression levels and in vitro sensitivity were analyzed.PPI, EVO, Pt, 5-FU and CPT-11 had anticancer effects on the freshly-removed gastric tumor tissues with average inhibition rates of 20.64%±14.25% for PPI, 21.14%±13.43% for EVO, 50.57%±22.37% for Pt, 53.54%±22.03% for 5-FU, and 39.33%±24.79% for CPT-11, respectively. Combination of PPI and Pt, EVO and Pt, EVO and 5-FU had higher inhibition rates than any single drug of them (P<0.001, P = 0.028, P = 0.017, respectively). The mRNA expression levels of ERCC1 were correlated with Pt sensitivity (rho = -0.645, P<0.001); the mRNA expression levels of TS were correlated with 5-FU sensitivity (rho = -0.803, P<0.001). There were also weak but significant correlations between APTX mRNA expression levels and CPT-11 sensitivity (rho = -0.376, P = 0.017) or EVO sensitivity (rho = -0.322, P = 0.036). ERCC1 mRNA expression levels was markedly suppressed by the presentation of PPI (P = 0.001) and slightly suppressed by the presentation of EVO (P = 0.04); whereas, TS mRNA expression levels was markedly decreased by the presentation of EVO (P = 0.017) and slightly decreased by the presentation of PPI (P = 0.047).PPI and EVO both could inhibit the activity of freshly-removed gastric tumor, and they could enhance the anticancer effect of Pt and 5-FU by reducing the mRNA expression levels of ERCC1 and TS

Computational Study on the Palladium-Catalyzed Allenylative Dearomatization Reaction

The detailed mechanism of the Pd-catalyzed coupling of naphthalene allyl chloride with allenyltributylstannane, resulting in the dearomatization of the naphthalene group, has been studied using density functional theory (DFT) calculations at the B3LYP level. The catalyst cycle can be divided into three main stages involving oxidative addition, transmetalation, and reductive elimination, none of which contains significantly large barriers. It is found that the oxidative addition takes place through a monophosphine pathway. The transmetalation step is responsible for the formation of the propargylic dearomatized product, due to the orientation of the metal-coordinated allenyl ligand. Reductive elimination of the dearomatized product from the intermediate (η³-allylnaphthalene)­(η¹-allenyl)­PdPH₃ occurs by coupling of the terminal carbon of the η¹-allenyl ligand with the ortho carbon of the η³-naphthalene ligand. Furthermore, it is shown that dichloromethane as solvent does not change the mechanistic picture significantly

Whole genome sequencing reveals translocation breakpoints disrupting TP63 gene underlying split hand/foot malformation in a Chinese family

Abstract Background Split hand/foot malformation (SHFM) is a congenital limb developmental disorder, which impairs the fine activities of hand/foot in the affected individuals seriously. SHFM is commonly inherited as an autosomal dominant disease with incomplete penetrance. Chromosomal aberrations such as copy number variations and translocations have been linked to SHFM. This study aimed to identify the genetic cause for three patients with bilateral hand and foot malformation in a Chinese family. Methods Karyotyping, single‐nucleotide polymorphism (SNP) array, whole exome sequencing, whole genome sequencing, and Sanger sequencing were applied to identify the pathogenic variant. Results Karyotyping revealed that the three patients had balanced reciprocal translocation, 46, XX, t(3;15) (q29;q22). SNP array identified no pathogenic copy number variation in the proband. Trio‐WES (fetus–mother–father) sequencing results revealed no pathogenic variants in the genes related to SHFM. Whole‐genome low‐coverage mate‐pair sequencing (WGL‐MPS), breakpoint PCR, and Sanger sequencing identified the breakpoints disrupting TP63 in the patients, but not in healthy family members. Conclusion This study firstly reports that a translocation breakpoint disrupting TP63 contributes to the SHFM in a Chinese family, which expands our knowledge of genetic risk and counseling underlying SHFM. It provides a basis for genetic counseling and prenatal diagnosis (preimplantation genetic diagnosis) for this family