Biological evaluation of 2,3-dioxoindolin-N-phenylacetamide derivatives as potent CDC25B and PTP1B phosphatase inhibitors

A series of 2,3-dioxoindolin-N-phenylacetamide derivatives was evaluated for inhibitory activity against CDC25B and PTP1B enzymes. Most of the derivatives showed inhibitory activity against CDC25B (IC50 = 3.2-23.2 µg/mL) and PTP1B (IC50 = 2.9-21.4 µg/mL). Compound 2h showed the most inhibitory activity in vitro with IC50 values of 3.2 and 2.9 µg/mL against CDC25B and PTP1B, respectively, compared with the reference drugs Na3VO4 (IC50 = 2.7 µg/mL) and oleanolic acid (IC50 = 2.3 µg/mL). The results of selectivity experiments showed that the 2,3-dioxoindolin-N-phenylacetamide derivatives were selective inhibitors against CDC25B and PTP1B. Enzyme kinetic experiments demonstrated that compound 2h was a specific inhibitor with the typical characteristics of a mixed inhibitor. In cytotoxic activity assays compound 2h had potent activity against A549, HeLa, and HCT116 cell lines. In addition, compound 2h showed potent tumor inhibitory activity in a colo205 xenograft model in vivo.

A biomechanical study on proximal junctional kyphosis following long-segment posterior spinal fusion.

Posterior long-segment spinal fusion may lead to proximal junctional kyphosis (PJK). The present study sought to identify the appropriate fusion levels required in order to prevent PJK using finite element analysis. A finite element model was constructed based on the whole-spine computed tomography findings of a healthy adult. Nine commonly used posterior spinal fusion methods were selected. Stress on the annulus fibrosis fibers, the posterior ligamentous complex, and the vertebrae after various spinal fusions in the upright position were compared. This study was divided into two groups: non-fusion and fusion. In the former, the stress between the T10 and the upper thoracic vertebrae was higher. Comparing thoracic and lumbar segments in the fusion group, the peak stress values of the upper instrumented vertebrae (UIV) were mainly observed in T2 and L2 whilst those of the UIV+1 were observed in T10 and L2. After normalization, the peak stress values of the UIV and UIV+1 were located in T2 and L2. Similarly, the peak stress values of the annulus fibrosus at the upper adjacent level were on T10 and L2 after normalization. However, the peak stress values of the interspinal/supraspinal complex forces were concentrated on T11, T12, and L1 after normalization whilst the peak stress value of the pedicle screw was on T2. Controversy remains over the fusion of T10, and this study simulated testing conditions with gravitational loading only. However, further assessment is needed prior to reaching definitive conclusions.

A biomechanical study on proximal junctional kyphosis following long-segment posterior spinal fusion

Posterior long-segment spinal fusion may lead to proximal junctional kyphosis (PJK). The present study sought to identify the appropriate fusion levels required in order to prevent PJK using finite element analysis. A finite element model was constructed based on the whole-spine computed tomography findings of a healthy adult. Nine commonly used posterior spinal fusion methods were selected. Stress on the annulus fibrosis fibers, the posterior ligamentous complex, and the vertebrae after various spinal fusions in the upright position were compared. This study was divided into two groups: non-fusion and fusion. In the former, the stress between the T10 and the upper thoracic vertebrae was higher. Comparing thoracic and lumbar segments in the fusion group, the peak stress values of the upper instrumented vertebrae (UIV) were mainly observed in T2 and L2 whilst those of the UIV+1 were observed in T10 and L2. After normalization, the peak stress values of the UIV and UIV+1 were located in T2 and L2. Similarly, the peak stress values of the annulus fibrosus at the upper adjacent level were on T10 and L2 after normalization. However, the peak stress values of the interspinal/supraspinal complex forces were concentrated on T11, T12, and L1 after normalization whilst the peak stress value of the pedicle screw was on T2. Controversy remains over the fusion of T10, and this study simulated testing conditions with gravitational loading only. However, further assessment is needed prior to reaching definitive conclusions.

Further characterization of o-nitrobenzaldehyde degrading bacterium Pseudomonas sp: ONBA-17 and deduction on its metabolic pathway

A previously reported o-nitrobenzaldehyde (ONBA) degrading bacterium Pseudomonas sp. ONBA-17 was further identified and characterized. Based on results of DNA base composition and DNA-DNA hybridization, the strain was identified as P. putida. Its degradation effect enhanced with increase of inoculum amount and no lag phase was observed. Higher removal rate was achieved under shaking conditions. All tested ONBA with different initial concentrations could be completely degraded within 5 d. In addition, degradative enzyme(s) involved was confirmed as intra-cellular distributed and constitutively expressed. Effects of different compounds on relative activity of degradative enzyme(s) within cell-free extract were also evaluated. Finally, 2-nitrobenzoic acid and 2, 3-dihydroxybenzoic acid were detected as metabolites of ONBA degradation by P. putida ONBA-17, and relevant metabolic pathway was preliminary proposed. This study might help with future research in better understanding of nitroaromatics biodegradation.

Further characterization of o-nitrobenzaldehyde degrading bacterium Pseudomonas sp: ONBA-17 and deduction on its metabolic pathway

A previously reported o-nitrobenzaldehyde (ONBA) degrading bacterium Pseudomonas sp. ONBA-17 was further identified and characterized. Based on results of DNA base composition and DNA-DNA hybridization, the strain was identified as P. putida. Its degradation effect enhanced with increase of inoculum amount and no lag phase was observed. Higher removal rate was achieved under shaking conditions. All tested ONBA with different initial concentrations could be completely degraded within 5 d. In addition, degradative enzyme(s) involved was confirmed as intra-cellular distributed and constitutively expressed. Effects of different compounds on relative activity of degradative enzyme(s) within cell-free extract were also evaluated. Finally, 2-nitrobenzoic acid and 2, 3-dihydroxybenzoic acid were detected as metabolites of ONBA degradation by P. putida ONBA-17, and relevant metabolic pathway was preliminary proposed. This study might help with future research in better understanding of nitroaromatics biodegradation.

Further characterization of o-nitrobenzaldehyde degrading bacterium Pseudomonas sp. ONBA-17 and deduction on its metabolic pathway.

A previously reported o-nitrobenzaldehyde (ONBA) degrading bacterium Pseudomonas sp. ONBA-17 was further identified and characterized. Based on results of DNA base composition and DNA-DNA hybridization, the strain was identified as P. putida. Its degradation effect enhanced with increase of inoculum amount and no lag phase was observed. Higher removal rate was achieved under shaking conditions. All tested ONBA with different initial concentrations could be completely degraded within 5 d. In addition, degradative enzyme(s) involved was confirmed as intra-cellular distributed and constitutively expressed. Effects of different compounds on relative activity of degradative enzyme(s) within cell-free extract were also evaluated. Finally, 2-nitrobenzoic acid and 2, 3-dihydroxybenzoic acid were detected as metabolites of ONBA degradation by P. putida ONBA-17, and relevant metabolic pathway was preliminary proposed. This study might help with future research in better understanding of nitroaromatics biodegradation.

Predicting the factors of lateral lymph node metastasis in papillary microcarcinoma of the thyroid in eastern China.

INTRODUCTION: Lateral lymph node metastasis is common in papillary thyroid microcarcinoma (PTMC). The present study evaluated the clinicopathologic characteristics and ultrasonographic (US) findings in predicting lateral LNM from PTMC in eastern China. MATERIALS AND METHODS: A total of 176 patients with confirmed PTMC by final histological examination who underwent central lymph node dissection (LND) and lateral LND were enrolled in our study. The clinicopathological and US data from the cases were analyzed retrospectively to determine the independent predictive factors for lateral LNM. Then, a scoring system was developed on the basis of independent factors. The sum of the points for individuals was evaluated for the value in predicting lateral LNM. RESULTS: Central LNM, underlying Hashimoto's thyroiditis, upper pole location, no well-defined margin and presence of calcifications were independent predictive factors for lateral LNM on multivariate analysis. Clinicopathological and US index points were statistically significant, with ≤ 2 favoring lateral LNM negativity with a sensitivity of 83.3 %, positive predictive value of 89.6 % and negative predictive value of 72.9 %. CONCLUSIONS: When the evaluation for lateral lymph nodes from a preoperative approach is inadequate or not obvious, our scoring system for prediction of lateral LNM can be another choice. Patients with clinicopathological and US index points ≤ 2 could be considered as lateral LNM negative, so more diagnostic approach is recommended for patients with clinicopathological and US index points >2.