Anti-epileptic and Neuroprotective Effects of Ultra-low Dose NADPH Oxidase Inhibitor Dextromethorphan on Kainic Acid-induced Chronic Temporal Lobe Epilepsy in Rats.

Neuroinflammation mediated by microglia and oxidative stress play pivotal roles in the development of chronic temporal lobe epilepsy (TLE). We postulated that kainic acid (KA)-Induced status epilepticus triggers microglia-dependent inflammation, leading to neuronal damage, a lowered seizure threshold, and the emergence of spontaneous recurrent seizures (SRS). Extensive evidence from our laboratory suggests that dextromethorphan (DM), even in ultra-low doses, has anti-inflammatory and neuroprotective effects in many animal models of neurodegenerative disease. Our results showed that administration of DM (10 ng/kg per day; subcutaneously via osmotic minipump for 4 weeks) significantly mitigated the residual effects of KA, including the frequency of SRS and seizure susceptibility. In addition, DM-treated rats showed improved cognitive function and reduced hippocampal neuronal loss. We found suppressed microglial activation-mediated neuroinflammation and decreased expression of hippocampal gp91phox and p47phox proteins in KA-induced chronic TLE rats. Notably, even after discontinuation of DM treatment, ultra-low doses of DM continued to confer long-term anti-seizure and neuroprotective effects, which were attributed to the inhibition of microglial NADPH oxidase 2 as revealed by mechanistic studies.

Prevention and management of vaginal cuff dehiscence: an updated review.

PURPOSE OF REVIEW: Minimally invasive hysterectomy has gained popularity because of its many benefits. However, laparoscopic and robotic assisted hysterectomy have been associated with increased risk of vaginal cuff dehiscence. This review is meant to address risk management and prevention of vaginal cuff dehiscence in patients undergoing minimally invasive hysterectomy. RECENT FINDINGS: Recent findings in the literature focus on addressing modifiable risk factors in patients and on using good surgical technique to help minimize the risk of vaginal cuff dehiscence. SUMMARY: The focus of this review is to help surgeons identify patient risk factors and address them preoperatively and to review surgical techniques that can minimize the risk of vaginal cuff dehiscence.

Development and Validation of a Nomogram Model Based on Hematological Indicators for Predicting the Prognosis of Diffused Gliomas.

Background: Diffused gliomas are aggressive malignant brain tumors. Various hematological factors have been proven to predict the prognosis of patients with gliomas. The aim of this study is to integrate these hematological markers and develop a comprehensive system for predicting the prognosis of patients with gliomas. Method: This retrospective study included 723 patients pathologically diagnosed with diffused gliomas. Hematological indicators were collected preoperatively, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), albumin globulin ratio (AGR), platelet distribution width (PDW), red blood cell distribution width (RDW), fibrinogen (FIB), and prognostic nutritional index (PNI). Least absolute shrinkage and selection operator (LASSO) Cox was applied to screen the hematological indicators for a better prediction of patients' prognosis and to build an inflammation-nutrition score. A nomogram model was developed to predict the overall survival (OS), which included age, tumor grade, IDH-1 mutations, and inflammation-nutrition score. Result: Patients were randomly divided into a primary cohort (n = 509) and a validation cohort (n = 214). There was no difference in age and IDH-1 mutation frequency between the cohorts. In the primary cohort, NLR, LMR, AGR, FIB, and PNI were selected to build an inflammation nutrition score. Patients with a high-risk inflammation-nutrition score had a short median OS of 17.40 months compared with 27.43 months in the low-risk group [HR 2.54; 95% CI (1.91-3.37); p < 0.001]. Moreover, age, tumor grade, IDH-1 mutations, and inflammation-nutrition score were independent prognostic factors in the multivariate analysis and thus were included in the nomogram model. The nomogram model showed a high prediction value with a Harrell's concordance index (C-index) of 0.75 [95% CI (0.72-0.77)]. The validation cohort supported these results. Conclusion: The prognostic nomogram model provided a high prognostic predictive power for patients with gliomas.

Investigation of binding characteristics of ritonavir with calf thymus DNA with the help of spectroscopic techniques and molecular simulation.

The binding behavior of ritonavir (RTV), a HIV/AIDS protease inhibitor, with ct-DNA was characterized through multiple testing technologies and theoretical calculation. The findings revealed that the RTV-DNA complex was formed through the noncovalent interaction mainly including conventional hydrogen bonds and carbon hydrogen bonds as well as hydrophobic interactions (pi-alkyl interactions). The stoichiometry and binding constant of the RTV-DNA complex were 1:1 and 1.87 × 103 M-1 at 298 K, respectively, indicating that RTV has moderate affinity with ct-DNA. The findings confirmed that RTV binds to the minor groove of DNA. The outcomes of CD experiments showed that the binding with RTV changed the conformation of DNA slightly. However, the conformation of RTV had obvious changes after binding to DNA, meaning that the flexibility of RTV molecule played an important role in stabilizing the RTV-DNA complex. Meanwhile, the results of DFT calculation revealed that the RTV and DNA interaction caused the changes in the frontier molecular orbitals, dipole moment and atomic charge distribution of RTV, altering the chemical properties of RTV when it bound to DNA. Communicated by Ramaswamy H. Sarma.

Water-Soluble Total Flavonoids Isolated from Isodon lophanthoides var. gerardianus (Benth.) H. Hara Promote Hepatocellular Carcinoma Sensitivity to 5-Fluorouracil.

Isodon lophanthoides var. gerardianus (Benth.) H. Hara, a native medicinal plant produced chiefly across Southern China, is one of the mainstream varieties of Xihuangcao, which has long been applied in preventing and treating some common liver or gall diseases. Water-soluble total flavonoids (WSTF) extracted from folk herbal medicine have many pharmacological effects. The objective of the paper is to investigate the synergy of WSTF with 5-fluorouracil (5-FU) on HCC and the related mechanisms. Cells were exposed to WSTF alone or combination treatment with 5-FU. Then, in this study, we conducted cell viability test, cell cycle and clone forming test, apoptosis assay, reactive oxygen species (ROS), Western blotting, immunohistochemistry, and a xenograft tumor growth model for investigating the role of WSTF in HCC in vivo and in vitro. It was discovered that WSTF caused cell cycle arrest at the G0/G1 phase while increasing the ROS contents. The generation of ROS levels could cause cell apoptosis and inhibit colony formation. WSTF decreased the Bcl-2 level but promoted the Bax level. These showed the mitochondrial dependence of WSTF-mediated apoptosis. WSTF combined with 5-FU have a synergistic effect to significantly inhibit carcinogenicity in vivo and in vitro. The reduced ROS changed the synergy of WSTF with 5-FU. At last, WSTF inhibit the growth of HCC and promote the HCC sensitivity to 5-FU through ROS accumulation. WSTF-increased ROS levels may partially or completely contribute to enhanced toxicity. WSTF combined with 5-FU in HCC can play a synergistic effect when applied in the clinical setting.

Evaluation of the interaction of novel tyrosine kinase inhibitor apatinib mesylate with bovine serum albumin using spectroscopies and theoretical calculation approaches.

Apatinib mesylate (APM), a novel tyrosine kinase inhibitor, has been applied in treating various cancers. In the present study, the binding mechanism of APM with bovine serum albumin (BSA) was studied by making use of various spectroscopic and theoretical calculation approaches to provide theoretical support for further studying its pharmacokinetics and metabolism. The results from fluorescence experiments showed that the quenching mechanism of BSA induced by APM was static quenching and the APM-BSA complex with the stoichiometry of 1:1 was formed during binding reaction. Moreover, the findings also showed that the binding process of APM to BSA was spontaneous and enthalpy-driven, and the mainly driving forces were hydrogen bonding, van der Waals as well as hydrophobic interactions. From the outcomes of the competitive experiments, it can be found that the binding site was primarily nestled in sub-domain IIIA of BSA (site II) which was in line with the results of molecular docking. An appreciable decline in α-helix content of BSA can be observed from the FT-IR data, meaning that the conformational change of BSA occurred after binding with APM, this phenomenon can be corroborated by the results of UV-vis, synchronous fluorescence and 3D fluorescence studies. Furthermore, the effect of some metal ions (e.g. K+, Co2+, Ni2+, Fe3+) on the binding constant of APM to BSA was explored.Communicated by Ramaswamy H. Sarma.

Insights on the interaction mechanism of brigatinib to human α-1-acid glycoprotein: Experimental and computational approaches.

Brigatinib, a multi-target kinase inhibitor, is primarily used to treat anaplastic lymphoma kinase (ALK)-positive patients with advanced non-small cell lung cancer (NSCLC) who have previously received crizotinib or are resistant to crizotinib. In this study, we focused on elucidating the interaction mechanism between brigatinib and human alpha-1-acid glycoprotein (HAG) through experimental and computational approaches. Steady-state fluorescence and UV-vis spectroscopy measurements revealed that brigatinib could quench the intrinsic fluorescence of HAG in a static quenching manner and formed the brigatinib-HAG complex with the stoichiometric ratio of 1:1. The findings revealed that brigatinib had a stronger affinity on HAG due to higher binding constant of 2.91 × 105 M-1 at 298 K. It can be proved from thermodynamic parameter analysis that brigatinib spontaneously bound to HAG in the means of enthalpy driven, the main forces for stabilizing brigatinib-HAG complexes were hydrogen bonding and hydrophobic interactions. The experimental results also indicated that the binding interaction induced micro-environmental changes around tryptophan residues and the alteration in secondary structure of HAG. The presence of metal ions like Mg2+, Zn2+, Ca2+, Ni2+ and Co2+ affects the binding interaction and thus change the therapeutic efficacy of brigatinib. Molecular docking results suggested that brigatinib was embedded to the hydrophobic cavity of HAG. The experimental and computational results certified that hydrogen bonding and hydrophobic interaction as well as electrostatic energy and van der Waals forces plays a leading role in the binding process.

Two highly oxygenated nor-clerodane diterpenoids from Croton caudatus.

Two highly oxygenated nor-clerodane diterpenoids, crocleropenes A and B (1 and 2), together with four known compounds (3-6) were isolated from the leaves and twigs of Croton caudatus. Their structures were elucidated by combination of extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. 1 and 2 represent the first examples of nor-clerodane-3,5(10)-diene diterpenoids. Compounds 1 and 2 exhibited weak cytotoxicity in vitro against MCF-7 cancer cells with IC50 values of 35.8 and 40.2 µM, respectively. [Formula: see text].

Removal of styrene in air stream by absorption combined with electrochemical oxidation.

Aqueous solution absorptions are widely used as an effective way for the treatment of noxious gases discharged from various industrial processes. However, this technology may encounter problems in removing gaseous pollutants with low Henry constants, such as styrene from contaminated air. In this study, a novel electrochemical absorption reactor was devised to remove these air pollutants. The reactor consists of five pairs of stacked mesh electrodes. Each pair of mesh electrodes consists of a Ti/RuO2 anode and a Ti cathode. The dimension of mesh electrode is 100 mm × 100 mm with 3 mm × 5 mm rhombic holes evenly distributed. The distance between two neighbouring electrodes is 25 mm. The simulated gas was introduced into the reactor from the bottom of the reactor by a gas distributor. The experimental result shows that styrene in the air was effectively removed by the electrochemical absorption reactor, and the removal increased with the increase of current density applied to the reactor. It was found that almost 100% styrene removal was achieved in 1% NaCl solution with 1 pH value and a current density of 0.04 A/cm2 applied to the reactor. The major liquid phase products from styrene oxidation were confirmed to be 1-Phenyl-1, 2-ethanediol and benzaldehyde.

Pulsed xenon ultraviolet and non-thermal atmospheric plasma treatments are effective for the disinfection of air in hospital blood sampling rooms.

BACKGROUND AND OBJECTIVES: Non-thermal atmospheric plasma treatment and pulsed xenon ultraviolet (PX-UV) treatment are widely used in disinfection of hospital environments. However, their effectiveness has not been evaluated against a comparator. The objective of this study is to evaluate their effectiveness in the disinfection of pathogens in the air in hospital blood sampling rooms. METHODS: Samples were taken from the air before and after disinfection with PX-UV and non-thermal atmospheric plasma. We counted bacterial colonies and identified the types of bacteria. RESULTS: Non-thermal plasma treatment significantly reduced bacterial counts in the air, the median reduced from 1 before treatment to zero afterwards (p = 0.03). PX-UV treatment also significantly reduced bacterial counts in the air (p = 0.01), the median reduced from 1.5 before treatment to zero afterwards. Pathogens identified in the current study include nosocomial bacteria, such as Staphylococcus aureus, Staphylococcus epidermidis, and yeast. CONCLUSION: Disinfection of blood sampling sites is essential in a health service department. The efficiency of PX-UV and non-thermal atmospheric plasma treatment are comparable in air disinfection.

Relationship between body mass index and incidence of breast cancer.

OBJECTIVE: To investigate the relationship between body mass index (BMI) and the breast cancer incidence, so as to making contribution to breast cancer screening in high-risk groups, to adjustment from passive medical treatment to active treatment Methods: BMI status of 206 breast cancer patients and that of 210 healthy subjects at different ages were compared and analyzed. RESULTS: The mean BMI was significantly higher in breast cancer patients than in healthy subjects 24.45±3.50 vs. 23.80±3.10 kg/m(2), t=-2.189, P=0.001. When stratified by age, BMI were significantly higher in ≥60 age for breast cancer than that of control group (Z=-3.408, P=0.001) and no significant difference in <60 years old .Logistic regression analysis showed that BMI was a risk factor of breast cancer (OR=1.886, 95% CI: 1.122-3.009). CONCLUSION: BMI have a relationship with the occurrence of breast cancer, especially for ≥60 years old.

Influence of the roughness, topography, and physicochemical properties of chemically modified surfaces on the heterogeneous nucleation of protein crystals.

In this study, the influence of some factors on the heterogeneous nucleation of hen egg-white lysozyme (E.C. 3.2.1.17) on a series of chemically modified surfaces has been investigated. Microbatch crystallization experiments were conducted on the microscope glass slides that were treated with poly-L-glutamic acid (PLG), poly(2-hydroxyethyl methacrylate) (P2HEMA), poly(methyl methacrylate) (PMMA), poly(4-vinyl pyridine) (P4VP), and (3-aminopropyl)triethoxysilane (APTES). An optical microscope with a heating/cooling stage was employed to measure the induction time of heterogeneous nucleation. The surface topography and roughness were characterized by atomic force microscopy. Contact angles for crystallization solution on the investigated surfaces were measured by a contact angle meter. From the theoretical analysis, the energetic barrier to heterogeneous nucleation was found to increase at higher contact angles and to decrease at higher roughness. Experimentally, a qualitative increase of the induction time of the heterogeneous nucleation on P2HEMA, APTES, and PMMA surfaces with the contact angle was observed. Such surfaces as P2HEMA, PLG, and APTES, which were of higher roughness, were shown to promote the heterogeneous nucleation. In addition, the surface with specific topography is expected to increase the possibility of the formation of a critical nucleus. Finally, the P4VP surface appeared to suppress the heterogeneous nucleation as a result of the electrostatic interaction between the lysozyme and P4VP molecules.

[Responses of microbial biomass P to the changes of organic C and P in paddy soils under different fertilization systems].

Based on a fifteen years field experiment in double rice-cropping region of subtropical China, the responses of microbial biomass P (MB-P) to organic C and P in red paddy soils under different fertilization systems were investigated. The results indicated that a long-term input of organic carbon sources and the increasing soil organic carbon made soil microbial biomass remain at a high level (MB-C > 800 mg x kg(-1)), being a main reason of the increase of MB-P. Under long-term zero chemical P fertilization, there was a significant decrease in soil total P (P < 0.05), but soil organic P increased by 29.3% on average. The inorganic P forms in deficit were mainly Al-P, Fe-P, Ca-P and O-P, with the lowest content of Al-P (only 0.5 mg x kg(-1) on average). The content of soil MB-P under zero chemical P fertilization was much higher than that of Olsen-P. Correlation analysis showed that there was a significant relationship (P < 0.05) between MB-P and Al-P, from which, it was deduced that the utilization of Al-P, Fe-P, Ca-P and O-P by soil microbes could be the key approach of promoting these P forms transformed into available P. Chemical P fertilization combined with organic nutrient recycling could not only enlarge the soil P pool, but also improve the P availability.