Intestinal barrier dysfunction is involved in the development of systemic inflammatory responses and lung injury in type A aortic dissection: a case-control study.

Background: The definite pathogenesis of lung injury complicated by type A aortic dissection (TAAD) remains unclear. In this paper, we investigated the relationship between intestinal injury, lung injury, and systemic inflammatory responses, with the aim of exploring the mechanism underlying intestinal injury and its impact on systemic inflammatory responses and lung injury in patients with TAAD. Methods: Patients with TAAD (n=36) and those with aortic root aneurysm (ARA) (n=30) were compared. TAAD patients were younger and had higher creatinine (Cr) than ARA patients. White blood cell (WBC) count, neutrophil count, neutrophil percentage, interleukin (IL)-6, IL-8, tumor necrosis factor α (TNF-α), C-reactive protein (CRP), histamine (HIS) levels, PaO2-FiO2 ratio, diamine oxidase (DAO), intestinal fatty acid binding protein (iFABP), and peptidoglycan (PGN) were measured using the same laboratory methods between the two groups. Results: Increased WBC [(9.70±4.05)×109/L vs. (5.88±1.2)×109/L, P<0.001], neutrophil [(7.65±4.27)×109/L vs. (3.40±0.97)×109/L, P<0.001], neutrophil percentage [(74.73±13.42)% vs. (57.67±9.45)%, P<0.001], IL-6 (37.48±4.87 vs. 20.90±0.92 pg/mL, P<0.001), IL-8 (97.15±9.11 vs. 69.46±3.17 pg/mL, P<0.001), TNF-α (71.32±10.35 vs. 33.90±2.27 pg/mL, P<0.001), CRP (10.67±1.62 vs. 4.43±0.26 µg/mL, P<0.001), HIS (13.29±1.88 vs. 7.63±0.58 ng/mL, P<0.001), DAO (24.94±4.72 vs. 10.92±2.44 U/L, P<0.001), iFABP (879.01±190.12 vs. 206.35±42.20 pg/mL, P<0.001), and PGN (31.10±5.51 vs. 12.52±2.20 ng/mL, P<0.001) and decreased PaO2-FiO2 ratio (365.35±146.47 vs. 447.86±70.80 mmHg, P=0.01) were detected in TAAD group relative to ARA group. In TAAD group, positive correlations were detected between DAO and inflammatory cytokines [IL-6 (r=0.56, P<0.001), IL-8 (r=0.61, P<0.001), TNF-α (r=0.71, P<0.001), and CRP (r=0.68, P<0.001)], between iFABP and inflammatory cytokines [IL-6 (r=0.72, P<0.001), IL-8 (r=0.71, P<0.001), TNF-α (r=0.90, P<0.001), and CRP (r=0.89, P<0.001)], between DAO and PGN (r=0.52, P<0.001), between iFABP and PGN (r=0.74, P<0.001), between PGN and inflammatory cytokines [IL-6 (r=0.85, P<0.001), IL-8 (r=0.44, P<0.001), TNF-α (r=0.61, P<0.001), and CRP (r=0.73, P<0.001)]. In acute TAAD subgroup, PGN and PaO2-FiO2 ratio were negatively correlated (r=-0.50, P=0.036). Conclusions: Systemic inflammatory responses in TAAD patients may lead to lung and intestine injury, and the latter may be involved in the development of systemic inflammatory responses and lung injury in these patients.

Perioperative management with biologics on severe aortic valve regurgitation caused by Behçet syndrome: the experience from a single center.

BACKGROUND: To investigate the efficacy and safety of biologics in the perioperative management of severe aortic valve regurgitation (AR) caused by Behçet syndrome (BS). METHODS: We retrospectively analyzed 20 patients with severe AR caused by BS who were all treated with biologics during the perioperative period of cardiac surgeries in our center between February 2016 and October 2020. RESULTS: A total of 20 patients with severe AR were enrolled, including 19 males and 1 female, with a mean age of 39.1 ± 8.8 years and a median course of 8 [interquartile range (IQR) 5.25-10.00] years. Before biologic administration, 92.9% of the patients who underwent aortic valve replacement had failed conventional therapy and developed postoperative paravalvular leakage (PVL) at a median interval of 4 months. Biologics were administered with background glucocorticoids (GCs) and immunosuppressants during the perioperative period for 22 aortic valve surgeries, including preoperatively with a median interval of 3.5 (IQR 2.75-4.25) months in 13 cases and within 3 months postoperatively in 9 cases. After a median follow up of 21 (IQR 15-32) months, 2 out of 13 cases (15.4%) preoperatively, and 1 out of 9 cases (11.1%) postoperatively treated with biologics developed PVL, and the rest were event free. The Behçet's Disease Current Activity Form score improved significantly (7 versus 0, median, p < 0.0001). Decrease of erythrocyte sedimentation rate [25.0 (IQR 11.00-36.25) mm/h versus 6.5 (IQR 4.0-8.8) mm/h, p < 0.001], and C-reactive protein [20.77 (IQR 7.19-29.58) mg/l versus 1.53 (IQR 0.94-2.92) mg/l, p = 0.001] were achieved rapidly and effectively. The GC dosage tapered from 40 (IQR 30-60) mg/d to 10 (IQR 5-11.25) mg/d, p < 0.0001. Immunosuppressants were tapered in number and dosage in 6 (30%) and 20 patients (100%), respectively. No serious adverse event was observed. CONCLUSION: Our study suggests that biologics were effective and well tolerated for the perioperative management of severe and refractory AR caused by BS, which significantly reduced the occurrence of postoperative PVL and had favorable GC- and immunosuppressant-sparing effect.

A negative feedback model to explain regulation of SARS-CoV-2 replication and transcription

BackgroundCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a preliminary understanding of the replication and transcription mechanisms of SARS-CoV-2 has recently emerged, their regulation remains unclear. ResultsBased on reanalysis of public data, we propose a negative feedback model to explain the regulation of replication and transcription in--but not limited to--SARS-CoV-2. The key step leading to new discoveries was the identification of the cleavage sites of nsp15--an RNA uridylate-specific endoribonuclease, encoded by CoVs. According to this model, nsp15 regulates the synthesis of subgenomic RNAs (sgRNAs) and genomic RNAs (gRNAs) by cleaving transcription regulatory sequences in the body. The expression level of nsp15 determines the relative proportions of sgRNAs and gRNAs, which in turn change the expression level of nps15 to reach equilibrium between the replication and transcription of CoVs. ConclusionsThe replication and transcription of CoVs are regulated by a negative feedback mechanism that influences the persistence of CoVs in hosts. Our findings enrich fundamental knowledge in the field of gene expression and its regulation, and provide new clues for future studies. One important clue is that nsp15 may be an important and ideal target for the development of drugs (e.g. uridine derivatives) against CoVs.

Bacterial Quorum Sensing Molecules Promote Allergic Airway Inflammation by Activating the Retinoic Acid Response.

IgE and IgG1 production in the type 2 immune response is the characteristic feature of an allergic reaction. However, whether bacterial molecules modulate IgE and IgG1 production remains obscure. Here, we demonstrate that the bacterial quorum sensing molecules acyl homoserine lactones (AHLs) induce IgE and IgG1 production by activating the RARE (retinoic acid response element) response in dendritic cells (DCs) in vivo. DC-specific knockout of the retinoic acid transcriptional factor Rara diminished the AHL-stimulated type 2 immune response in vitro. AHLs altered DC phenotype, upregulated OX40L and IFN-I signature, and promoted T helper 2 cell differentiation in vitro. Finally, AHLs activated the RARE response by inhibiting AKT phosphorylation in vitro, as the AKT agonists IGF-1 and PDGF abolished the effect of AHLs on the RARE response. This study demonstrates a mechanism by which AHLs drive allergic airway inflammation through activating retinoic acid signaling in DCs.

Corrigendum: Association Between D-dimer and Early Adverse Events in Patients With Acute Type A Aortic Dissection Undergoing Arch Replacement and the Frozen Elephant Trunk Implantation: A Retrospective Cohort Study.

[This corrects the article DOI: 10.3389/fphys.2019.01627.].

Precise annotation of human, chimpanzee, rhesus macaque and mouse mitochondrial genomes leads to insight into mitochondrial transcription in mammals.

In the present study, we applied our 'precise annotation' to the mitochondrial (mt) genomes of human, chimpanzee, rhesus macaque and mouse using 5' and 3' end small RNAs. Our new annotations updated previous annotations. In particular, our new annotations led to two important novel findings: (1) the identification of five Conserved Sequence Blocks (CSB1, CSB2, CSB3, LSP and HSP) in the control regions; and (2) the annotation of Transcription Initiation and novel Transcription Termination Sites. Based on these annotations, we proposed a novel model of mt transcription which can account for the mt transcription and its regulation in mammals. According to our model, Transcription Termination Sites function as switches to regulate the production of short, long primary transcripts and uninterrupted transcription, rather than simply terminate the mt transcription. Moreover, the expression levels of mitochondrial transcription termination factors control the proportions of rRNAs, mRNAs and lncRNAs in total mt RNA. Our findings point to the existence of many other, as yet unidentified, Transcription Termination Sites in mammals.

Association between cardiopulmonary bypass time and 90-day post-operative mortality in patients undergoing arch replacement with the frozen elephant trunk: a retrospective cohort study.

BACKGROUND: The aortic arch replacement and cardiopulmonary bypass (CPB) are both associated with the early mortality after cardiothoracic surgery. This study aimed to investigate the relationship between CPB time and 90-day post-operative mortality in patients undergoing aortic arch surgery using the frozen elephant trunk (FET) technique with selective ante-grade cerebral perfusion (SACP). METHODS: We retrospectively reviewed data of 377 adult patients undergoing aortic arch surgery via FET with SACP from July 1, 2017 to December 31, 2018 at Beijing Anzhen Hospital. The baseline characteristics, intra-operative data, and post-operative data were collected. Univariate and multivariate Cox regression analyses were used to determine independent predictors of 90-day post-operative mortality. RESULTS: The 90-day post-operative mortality was 13.53%. The 78.51% of patients were men. There were 318 (84.35%) type A aortic dissections and 28 (7.43%) aortic aneurysms. Among those, 264 (70.03%) were emergency operations. Median CPB time was 202.0 (176.0, 227.0) min. Multivariate Cox regression analysis revealed that CPB time was independently associated with 90-day post-operative mortality after adjusting confounding factors (hazard ratio: 1.21/10 min increase in CPB time, 95% confidence interval: 1.15-1.27, P < 0.001). Kaplan-Meier analysis based on CPB time tertiles revealed that the top tertile (median 236.0 min) was associated with reduced survival rate compared with middle and bottom tertiles (P < 0.001). Each sub-group analysis based on the complexity of the underlying disease process showed similar associations between CPB time and 90-day post-operative mortality. CONCLUSIONS: CPB time remains a significant factor in determining 90-day post-operative mortality in patients undergoing aortic arch surgery using FET with SACP. Surgeons should be aware of the relationship between CPB time and 90-day post-operative mortality during operative procedures and avoid extended CPB time as far as possible.

NormExpression: An R Package to Normalize Gene Expression Data Using Evaluated Methods.

Data normalization is a crucial step in the gene expression analysis as it ensures the validity of its downstream analyses. Although many metrics have been designed to evaluate the existing normalization methods, different metrics or different datasets by the same metric yield inconsistent results, particularly for the single-cell RNA sequencing (scRNA-seq) data. The worst situations could be that one method evaluated as the best by one metric is evaluated as the poorest by another metric, or one method evaluated as the best using one dataset is evaluated as the poorest using another dataset. Here raises an open question: principles need to be established to guide the evaluation of normalization methods. In this study, we propose a principle that one normalization method evaluated as the best by one metric should also be evaluated as the best by another metric (the consistency of metrics) and one method evaluated as the best using scRNA-seq data should also be evaluated as the best using bulk RNA-seq data or microarray data (the consistency of datasets). Then, we designed a new metric named Area Under normalized CV threshold Curve (AUCVC) and applied it with another metric mSCC to evaluate 14 commonly used normalization methods using both scRNA-seq data and bulk RNA-seq data, satisfying the consistency of metrics and the consistency of datasets. Our findings paved the way to guide future studies in the normalization of gene expression data with its evaluation. The raw gene expression data, normalization methods, and evaluation metrics used in this study have been included in an R package named NormExpression. NormExpression provides a framework and a fast and simple way for researchers to select the best method for the normalization of their gene expression data based on the evaluation of different methods (particularly some data-driven methods or their own methods) in the principle of the consistency of metrics and the consistency of datasets.

A Study on the Pressure-Lowering Effect of the Multilayer Stent.

BACKGROUND: The objective of the study was to investigate the hemodynamic changes of the blood flow in the aneurysm model after the multilayer stent placement using the fluid dynamic method, to analyze the effectiveness and properties of the multilayer stent in the treatment of aortic aneurysms. METHODS: A water tank was filled with 5 L of experimental liquid after the circular flow pressure test platform with a glass aneurysm model, and a multilayer stent was built. Pressure at the middle part and the distal aneurysm neck part of the model was then measured. At each site, the pressure was measured 20 times at 1-min intervals, and the testing results were averaged for accuracy. RESULTS: Without the stent, mean pressure at the middle part and at the distal aneurysm neck part of the model was 11.19 ± 0.23 Kpa and 13.31 ± 0.28 Kpa, respectively. With the stent, the mean pressure decreased to 10.60 ± 0.27 Kpa and 12.60 ± 0.29 Kpa, and the average difference was 0.59 ± 0.15 Kpa and 0.71 ± 0.15 Kpa, respectively. CONCLUSIONS: After the placement of the multilayer stent, pressure inside the model at the middle part and distal neck part could both be diminished, yet the mean dropped pressure may be too small to be sufficient to cause significant impact on preventing the expansion of abdominal aortic aneurysm; therefore, the pressure-lowering effect of the multilayer stent for abdominal aortic aneurysm may not be ideal compared with the traditional covered stents.

Using Pan RNA-Seq Analysis to Reveal the Ubiquitous Existence of 5' and 3' End Small RNAs.

In this study, we used pan RNA-seq analysis to reveal the ubiquitous existence of both 5' and 3' end small RNAs (5' and 3' sRNAs). 5' and 3' sRNAs alone can be used to annotate nuclear non-coding and mitochondrial genes at 1-bp resolution and identify new steady RNAs, which are usually transcribed from functional genes. Then, we provided a simple and cost effective way for the annotation of nuclear non-coding and mitochondrial genes and the identification of new steady RNAs, particularly long non-coding RNAs (lncRNAs). Using 5' and 3' sRNAs, the annotation of human mitochondrial was corrected and a novel ncRNA named non-coding mitochondrial RNA 1 (ncMT1) was reported for the first time in this study. We also found that most of human tRNA genes have downstream lncRNA genes as lncTRS-TGA1-1 and corrected the misunderstanding of them in previous studies. Using 5', 3', and intronic sRNAs, we reported for the first time that enzymatic double-stranded RNA (dsRNA) cleavage and RNA interference (RNAi) might be involved in the RNA degradation and gene expression regulation of U1 snRNA in human. We provided a different perspective on the regulation of gene expression in U1 snRNA. We also provided a novel view on cancer and virus-induced diseases, leading to find diagnostics or therapy targets from the ribonuclease III (RNase III) family and its related pathways. Our findings pave the way toward a rediscovery of dsRNA cleavage and RNAi, challenging classical theories.

Using high-resolution annotation of insect mitochondrial DNA to decipher tandem repeats in the control region.

In this study, we used a small RNA sequencing (sRNA-seq) based method to annotate the mitochondrial genome of the insect Erthesina fullo Thunberg at 1 bp resolution. The high-resolution annotations cover both entire strands of the mitochondrial genome without any gaps or overlaps. Most of the new annotations were consistent with the previous annotations which had been obtained using PacBio full-length transcripts. Two important findings were that animals transcribe both entire strands of mitochondrial genomes and the tandem repeats in the control region of the E. fullo mitochondrial genome contains the repeated Transcription Initiation Sites (TISs) of the heavy strand. In addition, we found that the copy numbers of tandem repeats showed a great diversity within an individual, suggesting that mitochondrial DNA recombination occurs in an individual. In conclusion, the sRNA-seq based method uses 5' and 3' end small RNAs to annotate nuclear non-coding and mitochondrial genes at 1 bp resolution, and can be used to identify new steady RNAs, particularly long non-coding RNAs (lncRNAs). The high-resolution annotations of mitochondrial genomes can also be used to study the molecular phylogenetics and evolution of animals or to investigate mitochondrial gene transcription, RNA processing, RNA maturation and several other related topics. The complete mitochondrial genome sequence of E. fullo with the new annotations using the sRNA-seq based method is available at the NCBI GenBank database under the accession number MK374364. We publish our theories, methods, the high quality sRNA-seq and RNA-seq data (SRA: SRP174926) for extensive use.

Association Between D-dimer and Early Adverse Events in Patients With Acute Type A Aortic Dissection Undergoing Arch Replacement and the Frozen Elephant Trunk Implantation: A Retrospective Cohort Study.

Objective: In the present study, we investigated the associations between D-dimer levels at admission and early adverse events in patients with acute type A aortic dissection undergoing arch replacement and the frozen elephant trunk (FET). Methods: We retrospectively analyzed data of patients with acute type A aortic dissection undergoing aortic arch surgery and FET from July 2017 to December 2018 at Beijing Anzhen Hospital. D-dimer levels were evaluated within 24 h of admission. Multivariate Cox regression analysis was used to determine independent predictors of early postoperative adverse events. Results: A total of 347 patients were included in the study. The average age of the patients was 48.07 ± 10.56 years, with male predominance (79.25%). The incidence of 90-day postoperative adverse events was 18.7%, consisting of 14.7% mortality and 4.0% permanent neurological dysfunction (PND). The median D-dimer level was 1.95 ug/ml (interquartile range, 0.77-3.16 ug/ml). Multivariable Cox regression analysis revealed that D-dimer level was independently associated with 90-day postoperative adverse events after adjustment for confounding factors (hazard ratio = 1.19 per 10 ug/ml increase in D-dimer, 95% confidence interval: 1.01-1.41; P = 0.039). Kaplan-Meier analysis revealed that the highest tertile (median 6.27 ug/ml) had more 90-day postoperative adverse events compared with the median and lowest tertiles (P = 0.0014). Sub-analysis found that the association remained unchanged. Conclusion: Increased D-dimer levels at admission were associated with 90-day postoperative adverse events in patients with acute type A aortic dissection undergoing arch replacement and FET. These results may help clinicians optimize the risk evaluation and perioperative clinical management to reduce early adverse events. Key Question: Explore the relationship between D-dimer and early outcomes in patients with aortic dissection with arch replacement. Key Findings: Increased D-dimer at admission was associated with adverse events in patients with aortic dissection with arch surgery. Take-Home Message: The high-risk patients deserve close medical monitoring.

TaAAP6-3B, a regulator of grain protein content selected during wheat improvement.

BACKGROUND: The content of grain protein (GPC) in cereals is an important part of total protein in human food. Exploring and utilizing new GPC genes is one of the most effective approaches for wheat quality breeding. RESULTS: Three homoeologues of TaAAP6(-3A, 3B, 3D)were cloned by homology cloning from OsAAP6.Temporal and spatial expression analysis showed that TaAAP6homoeologues were preferentially expressed in developing grains, and TaAAP6-3B may play a major role in regulating GPC in wheat. Association analysis indicated thatTaAAP6-3B-I is significantly correlated with higher GPC than that of TaAAP6-3B-II for 115 wheat lines in all five environments. TaAAP6-3B-I, the favored allele of TaAAP6-3B, was preferentially expressed in preliminary developing grain stage. Two functional markers were developed to discriminate 197F2populations and the result showed that TaAAP6-3B-I (high-protein content) was completely dominant. Two cis-regulatory elements appear to be associated with high GPC were found in the 5'UTR of TaAAP6-3B-I.The change of the TaAAP6-3B locus types indicated that the gene was subjected to selection pressures during long process of artificial selection. CONCLUSIONS: TaAAP6-3B is a regulator of GPC and its favored allele TaAAP6-3B-I exhibits an obvious potential application in wheat high-GPC breeding.

DN604: A platinum(II) drug candidate with classic SAR can induce apoptosis via suppressing CK2-mediated p-cdc25C subcellular localization in cancer cells.

DN604, a carboplatin analogue with a functional dicarboxylato ligand, was deeply investigated to explore its ability to induce apoptosis as well as its antitumor mechanism of action. Both in vitro and in vivo assays indicated that DN604 could effectively inhibit cell viability of SGC-7901 gastric cancer cells and exhibited stronger antitumor activity than carboplatin and comparable activity to cisplatin. Significantly in contrast to cisplatin, DN604 resulted in negligible toxic effects in vivo with the same tumor growth inhibition effect as cisplatin. The mechanism study indicated that DN604 inhibited CK2-phosphorylated cdc25C activation to decrease p-cdc25C subcellular localization, leading to the inactivation of cdc2/Cyclin B and G2/M cell cycle arrest and apoptosis in SGC-7901 cancer cells. Our research revealed for the first time that the dicarboxylato ligand containing a suitable functional moiety as the leaving group in the platinum(II) complex can effectively induce cell cycle arrest and apoptosis via inhibiting key checkpoint proteins.

Hybrid of DNA-targeting Chlorambucil with Pt(IV) Species to Reverse Drug Resistance.

Two hybrids of Pt(IV) species were designed and prepared by addition of a chlorambucil unit to the axial positions of the Pt(IV) complexes derived from DN603 and DN604. In vitro studies of two hybrids against two pairs of cisplatin sensitive and resistant cancer cell lines indicated that compound 5 had superior antitumor activity to cisplatin and chlorambucil via suppressing DNA damage repair to reverse drug resistance. Mechanistic investigation suggested that the potent antitumor activity of compound 5 arose from its major suppression of CK2-mediated MRE11-RAD50-NBS1(MRN) complex promotion of DNA double-strand break (DSB) repair. In nude mice with A549/CDDP xenografts, compound 5 exhibited higher anticancer efficacy than cisplatin and chlorambucil by reversing drug resistance, displayed improved effectiveness, and had no toxicity effects. Overall, compound 5 is a promising drug candidate, which could promote the anticancer activity and reverse drug resistance by attenuating CK2-induced MRN-dependent DSB repair.

Oxidative DNA double strand breaks and autophagy in the antitumor effect of sterically hindered platinum(II) complexes in NSCLCs.

A series of novel platinum(II) complexes with (1R,2R)-N1,N2-diisobutyl-1,2-diaminocyclohexane as a carrier ligand, while N1,N2-diisobutyl moiety serving as steric hindrance were designed, synthesized and characterized. The in vitro biological assays demonstrated that complex 3 had increased cytotoxicity against lung cancer cells, especially non-small-cell lung cancer (NSCLC) compared to its mono-substituted complex 3a, indicating that the sterically hindered alkyl moieties have significant influences on its antitumor property. However, the mechanism still remains unclear. The further studies revealed that complex 3 could induce ROS overproduction, severe DNA double strands breaks and inhibit the activation of DNA damage repair proteins within nucleus, leading to cell-cycle arrest and cell death. Moreover, complex 3 could induce autophagy via the accumulation of autophagic vacuoles and alterations of autophagic protein expression. Interestingly, the ROS scavengers, N-acetyl-cysteine (NAC) could reverse complex 3-induced DNA double strands breaks and autophagic responses more significantly compared to complex 3a. The results demonstrated that the ROS generation plays an important role in the DNA double strands breaks and autophagic responses in the antitumor effect of complex 3 with N1,N2-diisobutyl moiety. Our study offered a novel therapeutic strategy and put new insights into the anticancer research of the complexes with N1,N2-diisobutyl moiety served as steric hindrance.

Reversal of cisplatin resistance in human gastric cancer cells by a wogonin-conjugated Pt(IV) prodrug via attenuating Casein Kinase 2-mediated Nuclear Factor-κB pathways.

Pt(IV) prodrugs, with two additional coordination sites in contrast to Pt(II) drugs, have been actively studied nowadays, for they can perform well in enhancing the accumulation and retention of the corresponding Pt(II) drugs in cancer cells. Our designed Pt(II) drug, DN604, was recently found to exhibit significant anticancer activity and low toxicity, while, wogonin, a naturally O-methylated flavones, has been widely investigated for its tumor therapeutic potential. Thus, two Pt(IV)-based prodrugs were derived by addition of a wogonin unit to the axial position of DN604 and its analogue DN603 via a linker group. In vitro cytotoxicity assay indicated that the resulting compound 8 not only inherited the genotoxicity of DN604 on gastric cancer cells, but also obtained the COX inhibitory property arising from wogonin. Further studies revealed that compound 8 caused the accumulation of ROS production and decreased the mitochondrial membrane potential (ΔΨm). The CK2α kinase activity assay, ChIP and luciferase assays showed that CK2 plays an important role in the blockade of compound 8 on activated NF-κB survival pathways, which were established for sensitivity of cancer cells to platinum drugs. Similarly in vivo, in nude mice with SGC-7901/cDDP xenografts, compound 8 improved the effectiveness of DN604 via reversing tumor resistance and maintaining low toxicity. Overall, compound 8 is a promising Pt(IV) prodrug, which could be used to promote the anticancer activity of its counterpart Pt(II) species and reverse drug resistance via attenuating CK2-mediated NF-κB pathways during platinum-based chemotherapies.