Protective Effects of Ursodeoxycholic Acid Against Oxidative Stress and Neuroinflammation Through Mitogen-Activated Protein Kinases Pathway in MPTP-Induced Parkinson Disease.

OBJECTIVES: Parkinson disease (PD) is the second most common neurodegenerative disorder, and no disease-modifying medications are available. Ursodeoxycholic acid (UDCA) has been shown to prevent neuronal damage; however, the effect of UDCA on PD is unclear. This study aimed to the role of UDCA on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. METHODS: Mice were divided into 3 experimental groups: the control group, MPTP group, and UDCA-treat group. Mice were tested for behavioral impairments, and slices at the level of the ventral midbrain were collected to perform hematoxylin and eosin and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and immunohistochemistry. To evaluate the levels of dopamine (DA), serotonin (5-HT), antioxidant markers, and inflammatory cytokines, enzyme-linked immunoassays were carried out. The protein (α-synuclein, p38, phospho-p38, c-Jun N-terminal kinase [JNK], and phospho-JNK) expression was examined adopting Western blot. RESULTS: We found that UDCA reduced the MPTP-induced degeneration of DA neurons, improved behavioral impairments, and decreased the protein level of α-synuclein, accompanied with increases of DA and 5-HT. In the present study, UDCA prevented DA neurons from MPTP toxicity with increased superoxide dismutase, catalase, glutathione, and decreased malondialdehyde levels. Ursodeoxycholic acid prevented DA neurons from MPTP toxicity with decreased levels of tumor necrosis factor α, interferon γ, and interleukin (IL)-1ß, IL-6, and IL-10. Our results demonstrated that UDCA inhibited the phosphorylation of JNK and p38MAPK. CONCLUSIONS: This study revealed protective effects of UDCA against oxidative stress and neuroinflammation through mitogen-activated protein kinases pathways in MPTP-induced PD, suggesting that UDCA may be a novel therapeutic candidate for PD.

Enhanced C-H bond activation by tuning the local environment of surface lattice oxygen of MoO3.

The lattice oxygen on transition metal oxides serves as a critical active site in the dehydrogenation of alkanes, whose activity is determined by electronic properties and environmental structures. Hydrogen affinity has been used as a universal descriptor to predict C-H bond activation, while the understanding of the environmental structure is ambiguous due to its complexity. This paper describes a combined theoretical and experimental study to reveal the activity of lattice oxygen species with different local structures, taking Mo-based oxides and C-H bond activation of low-carbon alkanes as model catalytic systems. Our theoretical work suggests that oxygen species with convex curvature are more active than those with concave curvature. Theoretically, we propose an interpretative descriptor, the activation deformation energy, to quantify the surface reconstruction induced by adsorbates with various environmental structures. Experimentally, a Mo-based polyoxometalate with the convex curvature structure shows nearly five times the initial activity than single-crystal molybdenum oxide with the concave one. This work provides theoretical guidance for designing metal oxide catalysts with high activity.

Data-Driven Interpretable Descriptors for the Structure-Activity Relationship of Surface Lattice Oxygen on Doped Vanadium Oxides.

Understanding the structure-activity relationship of surface lattice oxygen is critical but challenging to design efficient redox catalysts. This paper describes data-driven redox activity descriptors on doped vanadium oxides combining density functional theory and interpretable machine learning. We corroborate that the p-band center is the most crucial feature for the activity. Besides, some features from the coordination environment, including unoccupied d-band center, s- and d-band fillings, also play important roles in tuning the oxygen activity. Further analysis reveals that data-driven descriptors could decode more information about electron transfer during the redox process. Based on the descriptors, we report that atomic Re- and W-doping could inhibit over-oxidation in the chemical looping oxidative dehydrogenation of propane, which is verified by subsequent experiments and calculations. This work sheds light on the structure-activity relationship of lattice oxygen for the rational design of redox catalysts.

Morphological Characterization and Transcriptome Analysis of New Dwarf and Narrow-Leaf (dnl2) Mutant in Maize.

Lodging is the primary factor limiting high yield under a high plant density. However, an optimal plant height and leaf shape can effectively decrease the lodging risk. Here we studied an ethyl methanesulfonate (EMS)-induced dwarf and a narrow-leaf mutant, dnl2. Gene mapping indicated that the mutant was controlled by a gene located on chromosome nine. Phenotypic and cytological observations revealed that dnl2 showed inhibited cell growth, altered vascular bundle patterning, and disrupted secondary cell wall structure when compared with the wild-type, which could be the direct cause of the dwarf and narrow-leaf phenotype. The phytohormone levels, especially auxin and gibberellin, were significantly decreased in dnl2 compared to the wild-type plants. Transcriptome profiling of the internodes of the dnl2 mutant and wild-type revealed a large number of differentially expressed genes enriched in the cell wall biosynthesis, remodeling, and hormone biosynthesis and signaling pathways. Therefore, we suggest that crosstalk between hormones (the altered vascular bundle and secondary cell wall structure) may contribute to the dwarf and narrow-leaf phenotype by influencing cell growth. These results provide a foundation for DNL2 gene cloning and further elucidation of the molecular mechanism of the regulation of plant height and leaf shape in maize.

Ursodeoxycholic acid protects dopaminergic neurons from oxidative stress via regulating mitochondrial function, autophagy, and apoptosis in MPTP/MPP+-induced Parkinson's disease.

Neuroprotection targeting mitochondrial dysfunction has been proposed as a potential therapeutic strategy for Parkinson's disease (PD). Ursodeoxycholic acid (UDCA) has been shown to prevent neuronal damage; however, the role of UDCA in PD is poorly understood. This study aimed to investigate the neuroprotective effects of UDCA on PD and its underlying mechanisms. We used MPTP/MPP+-induced PD models, including MPTP-induced mice, primary cultures of mice mesencephalic neurons and MPP+-treated neuro-2a cells to examine the effects of UDCA on PD pathogenesis. The results showed that UDCA improved behavioral performance and protected dopaminergic neurons in MPTP mice. UDCA improved cell viability and decreased cell death in MPP+-treated cells. UDCA inhibited reactive oxygen species accumulation, mitochondrial membrane potential collapse, and ATP depletion in neuro-2a cells. UDCA improved movement dysfunction, ameliorated autophagic flux and alleviated apoptosis. Furthermore, UDCA could activate the AMPK/mTOR and PINK1/Parkin pathways. In conclusion, UDCA may improve PD by regulating mitochondrial function, autophagy, and apoptosis, involving AMPK/mTOR and PINK1/Parkin pathways. These results open new perspectives for pharmacological use of UDCA in PD.

Arsenic Trioxide Inhibits Proliferation of Rabbit Tenon's Capsule Fibroblasts After Trabeculectomy by Downregulating Expression of Extracellular Matrix Proteins.

PURPOSE: The purpose of this study was to study the effectiveness of arsenic trioxide (ATO) in regulation of trabeculectomy in an animal model. METHODS: This study was designed as random, comparative, and prospective study. Primary Tenon's capsule fibroblasts (TFs) were cultured and their viability after arsenic trioxide (ATO) treatment was detected using 3-(4, 5-dimethylthiazolyl-2-)-2, 5-diphenyltetrazoliumbromide (MTT) and bromodeoxyuridine incorporation (BrdU) assays. The dose of ATO was determined by 50% growth inhibition (IC50 values) and cell-cycle analysis. The expression of extracellular matrix (ECM) components and proliferating cell nuclear antigen (PCNA) was determined by Western blotting analysis. The status of filtration bleb was detected by hematoxylin and eosins (HE) stain. RESULTS: Based on the MTT and BrdU assays, IC50 values was observed in rabbit TFs (rTFs) cells after treatment with ATO at a concentration of 6 µM arsenic trioxide for 72 hours. In addition, the ATO treatment caused not only a significant reduction in the expression of ECM proteins, fibronectin, collagen IV, and laminin in rTFs, but also reduced the expression of PCNA expression in a time dependent manner. The histologic observation showed high-level proliferation of rTFs in both vehicle and control groups, and proliferative ability of rTFs of experimental group was less than in vehicle and control group. Moreover, no inflammation was observed in the experimental group, and the filtering bleb was detected in the experimental group after 14 days of trabeculectomy. CONCLUSIONS: Arsenic trioxide inhibited the proliferation of rTFs after trabeculectomy and may improve the success ratio of trabeculectomy in an animal model.

[Effect of integrated measures on schistosomiasis transmission--interruption in hilly areas].

OBJECTIVE: To evaluate the effect of control integrative measures which persist in snail eradication and chemotherapy on schistosomiasis transmission-interruption in hilly areas. METHODS: The data of integrated control and endemic situation of schistosomiasis from 2004 to 2014 were collected, and the control effect of integrated measures was evaluated. RESULTS: From 2004 to 2014, both the Oncomelania hupensis snail area and density of living snails of Jurong City were reduced from 43.13 hm2 and 1.48 snails/0.1 m2 to 0; the residents' seropositive rate declined continuously; the residents' and students' awareness rates on schistosomiasis control were increased from 88.43% and 82.04% to 92.56% and 95.74% respectively; the snail area was significantly negatively correlated with the coverage rate of snail control (r = -0.864, P < 0.05). CONCLUSIONS: In the hilly areas, the schistosomiasis control integrated measures which persist in snail eradication and chemotherapy could control the endemic situation rapidly and steadily, accelerating to achieve the goal of schistosomiasis transmission-interruption.

[Efficacy and safety comparison of different statins in elderly patients].

OBJECTIVE: To compare the efficacy and safety of atorvastatin, rosuvastatin and xuezhikang capsule in elderly. METHODS: A total of 314 60-to-94-year-old (average (73.6 ± 7.9) years old) patients who were given different doses and types of statins were divided into three groups: the atorvastatin group (108 patients), the rosuvastatin group (104 patients) and the xuezhikang capsule group (102 patients). The serum TG, TC, LDL-C, HDL-C,ALT and CK were examined before and after the treatment which lasted for at least 4 weeks. All patients were divided into moderate risk group (13, 12 and 21 patients respectively in 3 groups); high risk group (40, 44 and 48 patients respectively in 3 groups) and very high risk group (55, 48 and 33 patients respectively in 3 groups ) according to guidelines on prevention and treatment of dyslipidemia in chinese adults (2007 version). The rate of reaching target goal and the dose when reaching target levels in different risk stratification groups were calculated and compared. RESULTS: Serum TC, LDL-C and non-HDL-C were significantly reduced after the 4-week-treatment in all the three groups (P < 0.01). Serum LDL-C level before and after treatment were (3.14 ± 0.78)mmol/L vs. (2.14 ± 0.65)mmol/L in atorvastatin group (the arevage dose was (16.4 ± 4.8)mg/d), (2.92 ± 0.77)mmol/L vs. (1.96 ± 0.55)mmol/L in rosuvastatin group (the arevage dose was (8.7 ± 3.0) mg/d), and (2.70 ± 0.62)mmol/L vs. (2.16 ± 0.61) mmol/L in xuezhikang capsule group (the arevage dose was (0.9 ± 0.3) g/d ). Among all the three groups of patients, the cases of reaching target levels of LDL-C were 13, 11 and 20 in patients at moderate risk, were 38(95.0%), 38(86.4%) and 40 (83.3%) in patients at high risk, and were 22(40.0%), 30(62.5%) and 17(51.5%) in patients at very high risk. There were no statistical differences in the rate of reaching target levels of LDL-C, non-HDL-C and TC in the three groups and at different risks (P > 0.05). One patient in the atorvastatin group showed ALT level elevation >3 times of the upper limit of normal value, there was no patient with CK level elevation >5 times of the upper limit of normal value. CONCLUSION: Atorvastatin, rosuvastatin and xuezhikang capsule at low dose and/or standard dose are effective and safety in elderly patients.

[The clinical features of gastrointestinal bleeding complicating aortic stenosis].

OBJECTIVE: To deepen the understanding about Heyde's syndrome by investigating the clinical characteristics and prognosis of the patients with aortic valve stenosis complicating with gastrointestinal bleeding. METHODS: Patients with aortic valve stenosis and gastrointestinal bleeding coincidently admitted to our hospital from 2001 to 2011 were retrieved and analyzed. RESULTS: In all the 443 157 in-patients, 474 patients were diagnosed with aortic valve stenosis (0.11%, 474/443 157) and 14 patients (9 males and 5 females, aged 53-87 years old) with gastrointestinal bleeding coincidently(2.95%, 14/474). Among the 14 patients, 3 were moderate aortic valve stenosis, 11 severe aortic valve stenosis. The aortic valve peak flow velocity was 324-709 (480.54 ± 188.25) cm/s and the mean aortic valve pressure gradient was 21.04-91.56 (56.93 ± 29.90) mm Hg(1 mm Hg = 0.133 kPa).Heavy gastrointestinal bleeding was manifested in all the 14 patients with 1 of haematemesis and 13 of hematochezia.Hemoglobin (Hb) and red blood cell (RBC) count were significantly lower than the normal range [(69 ± 28) g/L and (2.71 ± 2.04)×10(12)/L, P < 0.05]. Their mean corpuscular volume(MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet(PLT) count, prothrombin time (PT) and international normalized ratio (INR) were in normal range [(90.21 ± 2.94) fl, (29.39 ± 1.99) pg, (327.57 ± 14.82) g/L, (185.13 ± 22.55)×10(9)/L, (11.4 ± 1.04) s and 1.22 ± 0.44, respectively]. Among all the 14 patients, 13 were over 65 years old and they all accepted gastrointestinal imaging (13/14).Vascular malformation of intestine was found in 6 patients with 4 lesions located in descending colon and 2 located in sigmoid colon.Hemorrhage foci were found in 2 patients with one of colon cancer, and another of duodenal ulcer, while no definite hemorrhage foci were found in the other 11 patients. A total of 6 patients with severe aortic valve stenosis underwent aortic valve replacement (AVR) successfully (6/11) and no recurrent gastrointestinal bleeding was ever found. Conservative treatment was performed in the other 5 patients with severe aortic valve stenosis (5/11) and resulted in sudden death in 2 patients (2/5). CONCLUSIONS: Prompt echocardiography and gastrointestinal endoscopy should be performed in the elderly patients with obscure gastrointestinal bleeding to facilitate the early diagnosis and treatment of Heyde's syndrome. AVR is a fundamental procedure to improve the prognosis of Heyde's syndrome.

[Oncomelania snail habitat characteristics and orientation analysis in hilly areas of Jurong City].

OBJECTIVE: To master the breeding and distribution of Oncomelania snails in hilly regions of Jurong City so as to provide the evidence for establishing the program of snail elimination. METHODS: The historical snail habitat environments and existing snail habitat environments in hilly areas of Jurong City were investigated according to the river systems. The geographic coordinate data of the acquisition historical and existing snail habitat environments were collected by GPS tools in the field, and the characteristics and distribution of snail habitats were analyzed by Google Earth position technology. RESULTS: A total of 399 historical snail habitat environments were investigated, and the total area was 2904.39 hm2, including 33 Class I environments with the area of 415.04 hm2, 33 Class II environments with the area of 323.19 hm2, 11 Class III environments with the area of 96.40 hm2, and 318 Class IV environments with the area of 1989.46 hm2. The environmental reformation rate was 14.29%. The Google Earth marked maps showed the aggregation relation between the distribution of existing and historical snail habitats and the water systems. CONCLUSION: The investigation has established the data-base of historical snail habitat environments and the space is marked on the Google Earth map, which could help the snail monitoring and to establish the program of snail elimination better.

[Analysis of epidemic situation of schistosomiasis at Kongqing Village in Jurong City, 2012].

OBJECTIVE: To understand the epidemic situation of schistosomiasis and control effect in mountainous regions in Jurong City. METHODS: According to the "Schistosomiasis Prevention and Control Practices" and the "Schistosomiasis Monitoring Work Program in Jiangsu Province", the density of Oncomelania hupensis snails, and the infection rates of residents and animals were investigated and the results were analyzed statistically. RESULTS: The area with snails was 8150 m2, and the snail density was 0.14 snial/0.1 m2. The positive rate of schistosomiasis serological tests was 3.2% in the residents, and the infection rate was 0 in animals. CONCLUSION: The epidemic situation of schistosomiasis in the mountainous regions of Jurong City presents a low prevalence, but the surveillance is still needed.

[Investigation of pinworm infection among kindergarten children in Jurong City, Jiangsu Province].

In order to understand pinworm infection of kindergarten children in Jurong City, Jiangsu Province, a total of 1 088 children were sampled for the survey from September 2011 to October 2012. The cellophane tape swab technique was used to examine pinworm eggs. The infection rate of pinworm was 1.1% (12/1 088). The rate in boys and girls was 1.3% (7/551) and 0.9% (5/537), respectively. Higher infection rate was in the senior class (1.4%, 5/370), and no significant difference was found with gender, as well as among different classes (P > 0.05). Evidently, pinworm prevalence is at a low level in the kindergarten children of Jurong.

[Effect of comprehensive schistosomiasis control in Bianmin River of Jurong City from 2000 to 2011].

OBJECTIVE: To evaluate the effect of comprehensive control of schistosomiasis in the Biamin River water system. METHODS: The distribution of Oncomelania snails and schistosome infections of residents and cattle were investigated longitudinally in Biamin River system from 2000 to 2011. RESULTS: After the comprehensive control of schistosomiasis, the average densities of infected snails decreased from 0.013 snails/0.1 m2 to 0, the average densities of living snails decreased from 7.43 snails/0.1 m2 to 0.38 snails/0.1 m2, the infected snail area decreased from 0.08 hm2 to 0, the snail area decreased from 17.84 hm2 to 10.57 hm2, and the crowd serological positive rate decreased from 6.90% to 0.96%. CONCLUSIONS: The snail habitats have been eliminated obviously by the comprehensive measures including concrete banks of rivers connecting with the Yangtze River. Thus the schistosomiasis situation has been controlled effectively. However, the snail spread from other schistosomiasis endemic places could not avoided, so we still need to strengthen the snail surveillance and snail control of the rivers connecting with the Yangtze River.

KLF6SV1 siRNA inhibits proliferation of human lens epithelial cells.

PURPOSE: To investigate whether transfection with Krüppel-like factor 6 splice variant 1 (KLF6SV1) siRNA can inhibit proliferation of human lens epithelial cell (HLEC). METHODS: Plasmid containing KLF6SV1 siRNA was used to decrease the level of KLF6SV1 protein in HLEC. The expression of protein27 kinase inhibition protein 1 (p27(kip1)) and proliferation cell nuclear antigen (PCNA) was tested with western blot. Cell proliferation was assayed by 3-(4,5-dimethylthiazolyl-2-)-2,5-diphenyltetrazoliumbromide (MTT) assay and bromodeoxyuridine (BrdU) incorporation. RESULTS: KLF6SV1 siRNA can decrease KLF6SV1 expression which leads to increased levels of p27(kip1) and decreased expression of PCNA in HLEC. Cells transfected with pKLF6SV1 siRNA showed less viability compared with the control group in vitro. CONCLUSIONS: KLF6SV1 siRNA can effectively inhibit HLEC proliferation. It can be regarded as a novel target to treat posterior capsular opacity (PCO).