Broad-spectrum kinome profiling identifies CDK6 upregulation as a driver of lenvatinib resistance in hepatocellular carcinoma.

Increasing evidence has demonstrated that drug resistance can be acquired in cancer cells by kinase rewiring, which is an obstacle for efficient cancer therapy. However, it is technically challenging to measure the expression of protein kinases on large scale due to their dynamic range in human proteome. We employ a lysine-targeted sulfonyl fluoride probe, named XO44, which binds to 133 endogenous kinases in intact lenvatinib-resistant hepatocellular carcinoma (HCC) cells. This analysis reveals cyclin-dependent kinase 6 (CDK6) upregulation, which is mediated by ERK/YAP1 signaling cascade. Functional analyses show that CDK6 is crucial in regulation of acquired lenvatinib resistance in HCC via augmentation of liver cancer stem cells with clinical significance. We identify a noncanonical pathway of CDK6 in which it binds and regulates the activity of GSK3ß, leading to activation of Wnt/ß-catenin signaling. Consistently, CDK6 inhibition by palbociclib or degradation by proteolysis targeting chimeras (PROTACs) is highly synergistic with lenvatinib in vitro. Interestingly, palbociclib not only exerts maximal growth suppressive effect with lenvatinib in lenvatinib-resistant HCC models but also reshapes the tumor immune microenvironment. Together, we unveil CDK6 as a druggable target in lenvatinib-resistant HCC and highlight the use of a chemical biology approach to understand nongenetic resistance mechanisms in cancer.

A novel FAM83H variant causes familial amelogenesis imperfecta with incomplete penetrance.

BACKGROUND: Amelogenesis imperfecta (AI) is known to be a monogenic genetic disease caused by a variety of genes demonstrating a wide spectrum of penetrance. FAM83H is reported to be involved in AI: however, whether FAM83H causes AI with incomplete penetrance is unclear. METHODS: Whole-exome sequencing was performed on two patients with AI, and putative disease-related variants were validated by Sanger sequencing. Bioinformatic and in vitro functional analyses were performed to functionally characterize the identified disease-causing variants. RESULTS: We identified a novel heterozygous nonsense variant of FAM83H (NM_198488: c.1975G > T, p.Glu659Ter); in vitro functional analysis showed that this mutant produced mislocalized proteins and was deleterious. Surprisingly, the clinical manifestations of each of the six individuals carrying this variant were different, with one carrier appearing to be completely asymptomatic for AI. CONCLUSION: Our findings expand the variant spectrum for FAM83H and the phenotypic spectrum for FAM83H-associated AI and suggest that FAM83H-mediated AI exhibits incomplete penetrance.

The monomer derivative of paeoniflorin inhibits macrophage pyroptosis via regulating TLR4/ NLRP3/ GSDMD signaling pathway in adjuvant arthritis rats.

OBJECTIVE: This study was aimed to investigate the effect of monomer derivative of paeoniflorin (MDP) on macrophage pyroptosis mediated by TLR4/NLRP3/GSDMD signaling pathway in adjuvant arthritis (AA) rats. METHOD: Wistar rats were divided into normal group, AA model group, MDP (50 mg/kg) group and MTX (0.5 mg/kg) group. The expression of TLR4, NLRP3 and GSDMD in macrophage were detected by immunofluorescence assay. The expression of TLR4 and the ratio of macrophage pyroptosis were analyzed by flow cytometry. Cell morphology was observed by scanning electron microscopy. The cytokine levels of IL-18 and IL-1ß were detected by ELISA. The expressions of proteins related to macrophage pyroptosis were detected by western blot. RESULTS: MDP has a therapeutic effect on rats AA by reducing the secondary inflammation and improving pathological changes. The results of X-ray imaging and ultrasound images showed that MDP could inhibit bone erosion, soft tissue swelling, and joint space narrowing. Macrophage pyroptosis was found in secondary inflammation of AA rats. The expressions of TLR4, MyD88, NLRP3, Caspase-1, ASC, and GSDMD-N in macrophage were increased, the levels of IL-18 and IL-1ß were enhanced, and the morphology of pyroptosis could be observed. MDP could inhibit macrophage polarization and macrophage pyroptosis, and down-regulated the cytokine levels of IL-18 and IL-1ß in AA rats. MDP could regulate the M1/M2 ratio, decreased the ratio of macrophage pyroptosis and down-regulated the expressions of TLR4, MyD88, NLRP3, Caspase-1, ASC, and GSDMD-N in vivo and in vitro. CONCLUSION: Abnormal activation of TLR4/NLRP3/GSDMD signaling pathway may be involved in macrophage pyroptosis in AA rats. The therapeutic effect of MDP on AA rats is related to the inhibition of macrophage pyroptosis by regulating the TLR4/NLRP3/GSDMD signaling pathway.

Residues of Reduced Herbicides Terbuthylazine, Ametryn, and Atrazine and Toxicology to Maize and the Environment through Salicylic Acid.

Terbuthylazine (TBA), ametryn (AME), and atrazine (ATZ) are triazine family herbicides. They are dominantly used in the field of cereal crops like wheat and maize for prevention of upland from annual gramineous and broad-leaved weeds, with attributes of weed efficiency broad spectrum and good market performance. Salicylic acid (SA) is a kind of natural plant growth regulator existing widely in the plant kingdom and participating in many physiological and defense processes. In this study, the effects of SA on the detoxification and degradation of herbicides TBA, AME, and ATZ in maize were investigated. When maize plants were exposed to 6 mg kg-1 of the triazine herbicides, the growth and chlorophyll concentration were reduced, while the membrane permeability increased. After maize was sprayed with 5 mg kg-1 SA, the herbicide-induced phytotoxicity was significantly assuaged, with the increased content of chlorophyll and decreased cellular damage in plants. Activities of several biomarker enzymes such as SOD, POD, and GST were repressed in the presence of SA. The concentration of the triazine herbicides in maize and the soil determined by high-performance liquid chromatography was drastically reduced by spraying SA. Using LC/Q-TOF-MS/MS, six metabolites and nine conjugates of AME in maize and soil were characterized. The relative contents of AME metabolites and conjugates in maize with SA were higher than those without SA. These results suggest that SA is able to promote the detoxification and decay of these triazine herbicides in maize and soil.

Nomograms for predicting progression-free survival and overall survival after surgery and concurrent chemoradiotherapy for glioblastoma: a retrospective cohort study.

BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumor in adults. The prognosis of GBM patients is poor. Even with active standard treatment, the median overall survival is only 14.6 months. It is therefore critical to ascertain recurrence and search for factors that influence the prognosis of GBM. This study aimed to screen the variables related to the progression-free survival (PFS) and overall survival (OS) of GBM patients undergoing surgery and concurrent chemoradiotherapy, as well as propose a nomogram for individual risk prediction based on preoperative imaging parameters and clinicopathological variables readily available in clinical practice. METHODS: We retrospectively analyzed 114 consecutive patients with GBM who underwent surgery and concurrent chemoradiotherapy at the Second Affiliated Hospital, Zhejiang University School of Medicine from January 1st, 2015, to June 1st, 2018. Twenty-four preoperative magnetic resonance imaging (MRI) parameters were extracted manually from the Picture Archiving and Communication System (PACS). Clinicopathological factors were extracted from the electronic medical record system (EMRS). Least absolute shrinkage and selection operator (LASSO) regression and Cox regression were used for feature selection and model prediction, respectively. The models were presented using nomograms, which were applied to identify the risk of recurrence and survival according to the score. The performance of the nomograms to predict PFS and OS was tested with C-statistics, calibration plots, and Kaplan-Meier curves. RESULTS: The results revealed that sex, Karnofsky performance score (KPS), O6-methylglucamine-DNA methyltransferase (MGMT) protein expression, number of adjuvant chemotherapy cycles with temozolomide (TMZ), and the MRI signature effectively predicted PFS; and sex, KPS, extent of surgery, number of TMZ cycles, and MRI signature effectively predicted OS. The nomogram revealed good discriminative ability (C-statistics: 0.81 for PFS and 0.79 for OS). In the nomogram of PFS, patients with a score greater than 122 were considered to have a high risk of recurrence. In the nomogram of OS, the cutoff score were 115 and 145, and then patients were classified as low, medium, and high risk. CONCLUSIONS: In conclusion, our nomograms can effectively predict the risk of recurrence and survival of GBM patients and thus can be a good guide for clinical practice.

Effects of a contusion load on spinal cord with different curvatures.

The cervical spine injury is a complicated procedure in the combination of different injury loads and postures. The aim of this study is to investigate the injury mechanism considering different types of cervical curvatures subjected to contusion loads. A finite element model of a cervical spinal cord was constructed. Gray matter, white matter and pia matter were modeled and hyperelastic material properties were assigned. Convergence analysis and validation analysis were carried out. The model was simulated in 3 different spinal curvatures and loaded by 2 directions with 4 compression degrees. The maximum von Mises stress in the whole model was concentrated in the pia matter in all loading cases. When investigating spinal cord injury, the pia matter must be considered. For all three curvatures, the stress in the gray matter and white matter was higher in front-to-back loading condition than that in back-to-front loading condition. The front-to-back impact may cause a larger damage. A back-to-front load damaged the structure around the central canal and a front-to-back contusion load damaged the anterior horn of the spinal cord at most time. From the view of the maximum stress, the lordotic curvature did not show significant buffering effect. However, the pathological curvature had large areas affected and the lordotic curvature showed some benefits to some degree from the view of stress distribution.

Effects of contusion load on cervical spinal cord: A finite element study.

Injury of cervical spine is a common injury of locomotor system usually accompanied by spinal cord injury, however the injury mechanism of contusion load to the spinal cord is not clear. This study aims to investigate its injury mechanism associated with the contusion load, with different extents of spinal cord compression. A finite element model of cervical spinal cord was established and two scenarios of contusion injury loading conditions, i.e. back-to-front and front-to-back loads, were adopted. Four different compression displacements were applied to the middle section of the cervical spinal cord. The distributions of von Mises stress in middle transverse cross section were obtained from the finite element analysis. For the back-to-front loading scenario, the stress concentration was found in the area at and near the central canal and the damage may lead to the central canal syndrome from biomechanical point of view. With the front-to-back load, the maximum von Mises stress located in central canal area of gray matter when subject to 10% compression, whilst it appeared at the anterior horn when the compression increased. For the white matter, the maximum von Mises stress appeared in the area of the anterior funiculus. This leads to complicated symptoms given rise by damage to multiple locations in the cervical spinal cord. The illustrative results demonstrated the need of considering different loading scenarios in understanding the damage mechanisms of the cervical spinal cord, particularly when the loading conditions were given rise by different pathophysiological causes.

Characteristics of Blood Transfusion During Induction Remission in Children With Acute Lymphoblastic Leukemia: A Single-Center Retrospective Investigation.

OBJECTIVE: To investigate the allogeneic blood transfusion (ABT) characteristics of children with acute lymphoblastic leukemia (ALL) in different risk stratification during vincristine, daunorubicin, L-asparaginase and prednisone (VDLP) induction remission. SUBJECTS AND METHODS: By referring to electronic medical records, the demographic characteristics, diagnosis, test, and treatment information including ABT were collected. According to the risk stratification of the CCCG-ALL-2015 protocol, ABTs between groups were compared, and the differences were statistically analyzed. RESULTS: One hundred sixty-three newly treated children with ALL were enrolled in this study, who received 643.5 U of red blood cells and 377.6 U of platelets (PLTs) during the VDLP. The amount of ABT in the intermediate-risk (IR) group (n=102) was significantly higher than that in the low-risk group (n=61), which were reflected in the red blood cells in the first half of VDLP (P=0.033) and the PLTs in the second half of VDLP (P<0.001). Meanwhile, the PLT counts in the IR group were significantly lower in the same period. The time node was bounded by the minimal residual disease test on the 19th day. CONCLUSIONS: Children in the IR group or with unsatisfactory induction may need more ABTs during the VDLP, and the relatively low PLT counts seem to contribute to this. The results of this study can provide a basis for patient blood management, as well as a reference for studying the long-term effects of ABT on children with ALL.

Behavior of Cross Arms Inserted in Concrete-Filled Circular GFRP Tubular Columns.

Fiber-reinforced polymer (FRP) materials nowadays have attracted much attention in both retrofitting of aged infrastructure and developing of new structural systems attributed to the outstanding mechanical properties. Extensive studies have been performed on concrete-filled glass FRP (GFRP) tubes for the potential application in piling, poles, highways overhead sign structures and bridge components. The new hybrid member also provides an alternative solution for traditional transmission structures. However, the connection between concrete-filled GFRP tubes and cross arms has not been fully understood. In this paper, an experimental study and theoretical analysis were conducted on the behavior of cross arms inserted in concrete-filled circular GFRP tubular columns. Steel bars with a larger stiffness in comparison with GFRP tubes were selected here for the cross arm to simulate a more severe scenario. The structural responses of the system when the cross arms were subjected to concentrated loads were carefully recorded. Experimental results showed that the concrete-filled GFRP tubes could offer a sufficient restraint to the deformation of the cross arm. No visible cracks were found on the GFRP tube at the corner of the cross arm where the stress and strain concentrated. Theoretical solutions based on available theories and equations were adopted to predict the displacement of the cross arms and a good agreement was achieved between the prediction results and experimental findings.

[Effect of different sandblasting conditions on the metal-ceramic bonding strength of Co-Cr alloy fabricated by selective laser melting technology].

OBJECTIVE: To investigate the effect of different sandblasting conditions on the metal-ceramic bonding strength of Co-Cr alloy fabricated by selective laser melting (SLM) technology. METHODS: A total of 63 specimens of Co-Cr alloy fabricated by SLM were prepared and randomly divided into nine groups (n=7). Each group was treated with different powder particles (A1=50 µm, A2=100 µm, and A3=150 µm) and pressures (B1=0.2 MPa, B2=0.4 MPa, and B3=0.6 MPa) in sandblasting. One sample was randomly selected from each group for microstructure observation by scanning electron microscope (SEM). Ceramic was fired at the center of the specimens. Metal-ceramic bonding strength was measured with universal testing machine. Results were statistically analyzed with SPSS 17.0 software. RESULTS: The mean bond strengths were as follows: Group A1B1: 27.22 MPa±0.95 MPa, Group A1B2: 27.58 MPa±0.47 MPa, Group A1B3: 26.80 MPa±0.71 MPa, Group A2B1: 27.54 MPa±0.78 MPa, Group A2B2: 30.75 MPa±0.43 MPa, Group A2B3: 26.93 MPa±0.88 MPa, Group A3B1: 28.18 MPa±0.93 MPa, Group A3B2: 29.55 MPa±0.57 MPa, and Group A3B3: 28.11 MPa±0.91 MPa. The particle factor of Al2O3 and the pressure factor of blasting showed statistical significance (P<0.05). An interaction was observed between the factors of particle and pressure (P<0.05). Mixed fracture mode of all specimens was observed after the shear strength test. CONCLUSIONS: In conclusion, metal-ceramic bonding strength reaches the maximum when specimens are sandblasted with 100 µm alumina oxide at 0.4 MPa pressure.

Degradation of the In-plane Shear Modulus of Structural BFRP Laminates Due to High Temperature.

The behavior of fiber reinforced polymer (FRP) composites at high temperature is a critical issue that needs to be clearly understood for their structural uses in civil engineering. However, due to technical difficulties during testing at high temperature, limited experimental investigations have been conducted regarding the thermal behavior of basalt fiber reinforced polymer (BFRP) composites, especially for the in-plane shear modulus of BFRP laminates. To this end, both an analytical derivation and an experimental program were carried out in this work to study the in-plane shear modulus of BFRP laminates. After the analytical derivation, the in-plane shear modulus was investigated as a function of the elastic modulus in different directions (0°, 45° and 90° of the load-to-fiber angle) and Poisson's ratio in the fiber direction. To obtain the in-plane shear modulus, the four parameters were tested at different temperatures from 20 to 250 °C. A novel non-contacting digital image correlation (DIC) sensing system was adopted in the high-temperature tests to measure the local strain field on the FRP samples. Based on the test results, it was found that the elastic moduli in different directions were reduced to a very low level (less than 20%) from 20 to 250 °C. Furthermore, the in-plane shear modulus of BFRP at 250 °C was only 3% of that at 20 °C.

Intranasal endoscopic prelacrimal recess approach for maxillary sinus inverted papilloma.

PURPOSE: This study aims to determine the indications and effectiveness of transnasal endoscopic prelacrimal recess approach (PLRA) in patients with maxillary sinus inverted papilloma (IP). METHODS: We retrospectively analyzed 71 patients treated in our institution for maxillary sinus IP between August 2008 and April 2015. 20 patients underwent endoscopic surgery via PLRA. All the patients who had postoperative follow-up for 3 years were enrolled. Demographic data, surgical technique, location of IP attachment, intra- and postoperative complications, follow-up duration and recurrence were recorded. RESULTS: The outpatient follow-up period was 3-10 years after surgery. Recurrence of IP was seen in 6 (8.5%) of 71 patients, including 1 patient in the PLRA group. The recurrence rate was 5% in the PLRA group. Six of 71 patients experienced postoperative complications, but none was observed in the PLRA group. CONCLUSION: Transnasal endoscopic PLRA is a minimally invasive, safe and effective method for maxillary sinus IP. The indication for PLRA is tumor pedicle located on the antero-inferior or infero-lateral wall or at multiple attachment sites of the maxillary sinus.

Jasmonic Acids Facilitate the Degradation and Detoxification of Herbicide Isoproturon Residues in Wheat Crops ( Triticum aestivum).

Jasmonic acid (JA) [or methyl-jasmonic acid (MeJA)] is one of the important regulators of plant growth, development, and defense with respect to environmental stresses, but how JA is involved in mediation of pesticide accumulation and degradation in plants is largely unknown. This study investigated the contribution of MeJA to detoxification and degradation of isoproturon (IPU) residues in wheat ( Triticum aestivum). Wheat plants were exposed to 4 mg of isoproturon kg-1 (environmentally realistic concentration). The level of growth and chlorophyll concentration were reduced, while the electrolyte permeability in plants was enhanced. When plants were sprayed with 0.1 µM MeJA, the phytotoxicity induced by isoproturon was significantly assuaged, which was manifested by an increased chlorophyll concentration and a reduced level of cellular damage in wheat. Activities of several stress marker enzymes with isoproturon were repressed in the presence of MeJA. We measured accumulation of isoproturon in wheat and its residues in soil by high-performance liquid chromatography. The concentration of isoproturon in wheat and soils with MeJA was drastically reduced. Using ultraperformance liquid chromatography-tandem mass spectrometry, 12 isoproturon derivatives (eight metabolites and four conjugates) in wheat were characterized. We further provided evidence that the concentration of endogenous MeJA was significantly increased in IPU-exposed plants. These results suggest that MeJA was able to detoxify or degrade isoproturon in wheat when grown in a realistic environmental isoproturon-polluted soil.

Critically dysregulated signaling pathways and clinical utility of the pathway biomarkers in lymphoid malignancies.

Accumulating evidence confirmed that many dysregulated signaling pathways and aberrant genetic alterations contribute to the oncogenesis and heterogeneity of lymphoid malignancies. Therapeutically targeting dysregulating signaling pathways and their hidden oncogenic biomarkers are becoming available, but did not show desired therapeutic effect in current clinical practice. It is meaningful to further understand the underlying mechanisms of the dysregulated signaling pathways and to address the potential utility of pathway-related biomarkers. To precisely identify the dysregulation of signaling pathways and the "driver" oncogenic biomarkers, as well as to develop reliable and reproducible risk-stratification based on biomarkers will be challenging. Nevertheless, pathway-based targeted therapy will raise the hope to improve the outcomes of the patients with lymphoid malignancies, especially with aggressive types, and the efficient utility of pathway-related biomarkers in diagnosis, prognosis, prediction of lymphoid malignancies may also be able to power precision medicine.

Genetic variants in CHEK1 gene are associated with the prognosis of thoracic esophageal squamous cell carcinoma patients treated with radical resection.

CHEK1 gene is known to play an important role in tumor progression by cell cycle control. However, the association between CHEK1 and the prognosis of esophageal squamous cell carcinoma (ESCC) is unclear. In this study, we explored the association between genetic variants in CHEK1 gene and prognosis of ESCC patients treated with radical resection. A total of 131 thoracic ESCC patients who underwent radical resection were included in this retrospective study and genotyped using the MassArray method. According to the univariate Cox hazard analysis, the GT/TT genotype of CHEK1 rs555752 was shown to be strongly related to a decreased overall survival (OS) (HR=2.560, 95% CI: 1.415-4.631, P=0.002) and disease-free survival (DFS) (HR=2.160, 95% CI: 1.258-3.710, P=0.005). Furthermore, according to the multivariate Cox hazard analysis and multiple testing, patients with the GT/TT genotype of CHEK1 rs555752 had a notably decreased OS (HR=2.735, 95% CI: 1.468-5.096, P=0.002, Pc=0.006) and DFS (HR=2.282, 95% CI: 1.292-4.023, P=0.004, Pc=0.012). In conclusion, genetic variants of the CHEK1 gene are significantly related to OS and DFS of ESCC patients, and may therefore be predictors of the prognosis of thoracic ESCC after surgery.

Predictive effects of bilirubin on response of colorectal cancer to irinotecan-based chemotherapy.

AIM: To examine the predictive effects of baseline serum bilirubin levels and UDP-glucuronosyltransferase (UGT) 1A1*28 polymorphism on response of colorectal cancer to irinotecan-based chemotherapy. METHODS: The present study was based on a prospective multicenter longitudinal trial of Chinese metastatic colorectal cancer (mCRC) patients treated with irinotecan-based chemotherapy (NCT01282658). Baseline serum bilirubin levels, including total bilirubin (TBil) and unconjugated bilirubin (UBil), were measured, and genotyping of UGT1A1*28 polymorphism was performed. Receiver operating characteristic curve (ROC) analysis was used to determine cutoff values of TBil and UBil. The TBil values were categorized into > 13.0 or ≤ 13.0 groups; the UBil values were categorized into > 4.1 or ≤ 4.1 groups. Combining the cutoff values of TBil and UBil, which was recorded as CoBil, patients were classified into three groups. The classifier's performance of UGT1A1*28 and CoBil for predicting treatment response was evaluated by ROC analysis. Associations between response and CoBil or UGT1A1*28 polymorphism were estimated using simple and multiple logistic regression models. RESULTS: Among the 120 mCRC patients, the serum bilirubin level was significantly different between the UGT1A1*28 wild-type and mutant genotypes. Patients with the mutant genotype had an increased likelihood of a higher TBil (P = 0.018) and a higher UBil (P = 0.014) level compared with the wild-type genotype. Patients were stratified into three groups based on CoBil. Group 1 was patients with TBil > 13.0 and UBil > 4.1; Group 2 was patients with TBil ≤ 13.0 and UBil > 4.1; and Group 3 was patients with TBil ≤ 13.0 and UBil ≤ 4.1. Patients in Group 3 had more than a 10-fold higher likelihood of having a response in the simple (OR = 11.250; 95%CI: 2.286-55.367; P = 0.003) and multiple (OR = 16.001; 95%CI: 2.802 -91.371; P = 0.002) analyses compared with the Group 1 individuals. Patients carrying the UGT1A1*28 (TA)7 allele were 4-fold less likely to present with a response compared with the individuals harboring a homozygous (TA)6 genotype in the simple (OR = 0.267; 95%CI: 0.100-0.709; P = 0.008) and multiple (OR = 0.244; 95%CI: 0.088-0.678; P = 0.007) analyses. Classifier's performance of CoBil and UGT1A1*28 were comparable. CONCLUSION: CoBil and UGT1A1*28 are both independent biomarkers for predicting the treatment response of mCRC patients to irinotecan-based chemotherapy. After validation, CoBil, an easily determinable index in the clinic, might be helpful in facilitating stratification of mCRC patients for individualized treatment options.

Towards muscle-specific meat color stability of Chinese Luxi yellow cattle: A proteomic insight into post-mortem storage.

Searching for potential predictors of meat color is a challenging task for the meat industry. In this study, the relationship between meat color parameters and the sarcoplasmic proteome of M. longissimuss lumborum (LL) and M. psoas major (PM) from Chinese Luxi yellow cattle during post-mortem storage (0, 5, 10 and 15days) were explored with the aid of the integrated proteomics and bioinformatics approaches. Meat color attributes revealed that LL displayed better color stability than PM during storage. Furthermore, sarcoplasmic proteins of these two muscles were compared between days 5, 10, 15 and day 0. Several proteins were closely correlated with meat color attributes and they were muscle-specific and responsible for the meat color stability at different storage periods. Glycerol-3-phosphate dehydrogenase, fructose-bisphosphate aldolase A isoform, glycogen phosphorylase, peroxiredoxin-2, phosphoglucomutase-1, superoxide dismutase [Cu-Zn], heat shock cognate protein (71kDa) might serve as the candidate predictors of meat color stability during post-mortem storage. In addition, bioinformatics analyses indicated that more proteins were involved in glycolytic metabolism of LL, which contributed to better meat color stability of LL than PM. The present results could provide a proteomic insight into muscle-specific meat color stability of Chinese Luxi yellow cattle during post-mortem storage.

Isolated gastric recurrence from ovarian carcinoma: A case report.

Although ovarian metastasis secondary to gastric cancer (Krukenberg tumor) has been extensively described in the literature, gastric metastasis from ovarian carcinoma is rare. The present case report describes a patient with gastric metastasis from ovarian carcinoma. A 51-year-old female with previously treated ovarian carcinoma of stage III according to the International Federation of Gynecology and Obstetrics was admitted to the Department of Oncology, First Affiliated Hospital of Nanjing Medical University (Nanjing, China) with high serum carbohydrate antigen-125 levels. Endoscopic ultrasound and 18F-fluorodeoxyglucose positron emission tomography/computed tomography scanning revealed a lesion in the stomach with the typical appearance of a gastrointestinal stromal tumor. The histopathological examination revealed infiltration of the resected specimens by metastatic serous adenocarcinoma and a comparison with the previously resected ovarian specimen confirmed disease recurrence. Although isolated gastric recurrence from ovarian carcinoma is rare, when a patient has a history of ovarian carcinoma (particularly with a high CA-125 level) and when the imaging results show a mass in the stomach wall, metastasis from ovarian carcinoma should be considered.

Mixed-ligand mononuclear copper(II) complex: crystal structure and anticancer activity.

A novel copper(II) complex with mixed ligands including ß-[(3-formyl-5-methyl-2-hydroxy-benzylidene)amino]propionic acid anion and 1,10'-phenanthroline was synthesized, and its crystal structure was thoroughly characterized. It exerted excellent inducing apoptosis, anti-angiogenesis and antiproliferative properties in vitro. The complex can bind human serum albumin (HSA) at physiological pH conditions. Remarkably, it can induce formation of the mixed parallel/antiparallel G-quadruplex structures in the G-rich sequence of the proximal vascular endothelial growth factor (VEGF) promoter, and stabilize these G-quadruplex structures, which provide an opportunity for anti-angiogenesis chemotherapeutics. Furthermore, the complex showed a strong uptake, and exhibited multiple anticancer functions by inhibiting the expression of p-Akt and p-Erk1/2 proteins and by upregulating the levels of reactive oxygen species (ROS). Because of the reported results, this new copper(II) complex qualifies itself as a potential anticancer drug candidate.

MiR-1 targets PIK3CA and inhibits tumorigenic properties of A549 cells.

MicroRNAs are small endogenous RNAs that play important roles in the pathogenesis of human diseases, including malignancy. MicroRNA-1 (miR-1) is downregulated in non-small cell lung cancer (NSCLC); however, the underlying mechanisms by which it suppresses tumorigenesis in NSCLC are largely unknown. We investigated whether phosphoinositide-3-kinase catalytic subunit alpha (PIK3CA) was a novel target of miR-1 in the NSCLC cell line A549, and the mechanism of miR-1 inhibition of the tumorigenic properties of A549 cells is discussed. The influence of miR-1 on A549 cells was studied by transfection with miR-1 mimics or inhibitor. MiR-1 overexpression led to downregulation of PIK3CA protein, but not mRNA by western blot and quantitative real-time PCR, respectively. The dual-luciferase reporter assay confirmed that miR-1 targeted PIK3CA directly. PIK3CA downregulation by miR-1 mimics led to a significant reduction of phosphorylated Akt and survivin protein, the downstream targets of the PI3K/Akt pathway. Cell proliferation was studied using a cell counting kit. Migration and invasion were evaluated by Transwell and Matrigel assays, respectively. Cell cycle and apoptosis were detected by flow cytometry. The results were that miR-1 upregulation inhibited A549 cell proliferation, migration, and invasion. These findings indicate that miR-1 may play an important role in the pathogenesis of NSCLC by regulating PIK3CA through the PI3K/Akt pathway. Increasing miR-1 expression may provide a novel approach for NSCLC treatment.