AMP-activated protein kinase α2 contributes to acute and chronic hyperuricemic nephropathy via renal urate deposition in a mouse model.

Hyperuricemia can induce acute and chronic kidney damage, but the pathological mechanism remains unclear. The potential role of AMP-activated protein kinase (AMPK) α2 in hyperuricemia-induced renal injury was investigated in this study. Acute and chronic hyperuricemic nephropathy was induced by administering intraperitoneal injections of uric acid and oxonic acid to AMPK α2 knockout and wild-type mice. Changes in renal function, histopathology, inflammatory cell infiltration, renal interstitial fibrosis, and urate deposition were analyzed. In both acute and chronic hyperuricemic nephropathy mouse models, knockout of AMPK α2 significantly reduced serum creatinine levels and renal pathological changes. The tubular expression of kidney injury molecule-1 was also reduced in hyperuricemic nephropathy mice deficient in AMPK α2. In addition, knockout of AMPK α2 significantly suppressed the infiltration of renal macrophages and progression of renal interstitial fibrosis in mice with chronic hyperuricemic nephropathy. Knockout of AMPK α2 reduced renal urate crystal deposition, probably through increasing the expression of the uric acid transporter, multidrug resistance protein 4. In summary, AMPK α2 is involved in acute and chronic hyperuricemia-induced kidney injury and may be associated with increased urate crystal deposition in the kidney.

Metformin improves renal injury of MRL/lpr lupus-prone mice via the AMPK/STAT3 pathway.

OBJECTIVE: Lupus nephritis (LN) is a major complication and cause of death among patients with SLE. This research used in vivo and in vitro experiments to explore the therapeutic potential of metformin in kidney injury from LN-induced inflammation. METHODS: In vivo study, 8-week-old MRL/MpJ-Faslpr/J (MRL/lpr) mice were randomly divided into two groups (n=12 each): daily administration of 0.3 mg/mL metformin in drinking water and control (water only). Body weight and urinary samples were measured biweekly. Mice were sacrificed after 8-week treatment to harvest serum, lymph nodes, spleen and kidneys. In vitro study, human kidney-2 (HK-2) cells were pretreated with 1 mM metformin for 1 hour and then stimulated with 20 µg/mL lipopolysaccharides (LPS) or 10 ng/mL tumour necrosis factor-α (TNF-α) for another 48 hours. Protein was collected for subsequent analysis. RESULTS: We found that metformin administration improved renal function in MRL/lpr lupus-prone mice, measured by decreased urea nitrogen and urinary proteins. Metformin reduced immunoglobulin G and complement C3 deposition in glomeruli. The treatment also downregulated systemic and renal inflammation, as seen in decreased renal infiltration of F4/80-positive macrophages and reduced splenic and renal MCP-1 (monocyte chemoattractant protein-1) and TNF-α, and renal IL-1ß (interleukin 1ß) expression. Metformin administration decreased renal expression of necroptosis markers p-RIPK1 (phosphorylated receptor-interacting protein kinase 1) and p-MLKL, along with tubular injury marker KIM-1 (kidney injury molecule-1) in lupus mice. In addition, metformin alleviated the necroptosis of HK-2 cells stimulated by LPS and TNF-α, evidencing by a decrease in the expression of necroptosis markers p-RIPK1, p-RIPK3 and p-MLKL, and the inflammasome-related markers NLRP3 (NLR family pyrin domain containing 3), ASC (apoptosis-associated speck-like protein containing a CARD), caspase-1. Mechanistically, metformin treatment upregulated p-AMPK (phosphorylated AMP-activated protein kinase) and downregulated p-STAT3 (phosphorylated signal transducer and activator of transcription 3) expression in the kidneys. Moreover, AMPKα2 knockdown abolished the protective effects of metformin in vitro. CONCLUSIONS: Metformin alleviated kidney injury in LN though suppressing renal necroptosis and inflammation via the AMPK/STAT3 pathway.

Full particle-in-cell simulation of the formation and structure of a collisional plasma shock wave.

The formation and structure of a collisional shock wave in a fully ionized plasma is studied via full particle-in-cell simulations, which allows the complex momentum and energy transfer processes between different charged particles to be treated self-consistently. The kinetic energy of the plasma flow drifting towards a reflecting piston is found to be rapidly converted into thermal motion under the cooperative effects of ion-ion collisions, ion-electron collisions, and electric field charged-particle interactions. The subsequent shock evolution is influenced by the "precursor" ion beam before a quasisteady state is reached. The shock wave structure is then analyzed from a two-fluid transport viewpoint, which is found to be affected by "flux-limiting" electron transport, the nonthermal ions, and the charge separation electric field.

China's new strategy to block Schistosoma japonicum transmission: experiences and impact beyond schistosomiasis.

Despite sustained efforts for its control made over the past 50+ years, the re-emergence of schistosomiasis in China was noted around the turn of the new millennium. Consequently, a new integrated strategy was proposed to stop the contamination of schistosome eggs to the environment, which emphasizes health education, access to clean water and adequate sanitation, mechanization of agriculture and fencing of water buffaloes, along with chemotherapy. Validation of this integrated control strategy in four pilot counties in the provinces of Anhui, Hubei, Hunan and Jiangxi revealed significant reductions in the rate of Schistosoma japonicum infection in humans and intermediate host snails. Importantly, this strategy showed an impact on diseases beyond schistosomiasis, signified by concomitant reductions in the prevalence of soil-transmitted helminth infections. In view of China's new integrated strategy for transmission control of schistosomiasis showing an ancillary benefit on other helminthic diseases, we encourage others to investigate the scope and limits of integrated control of neglected tropical diseases.

Continuous fluoxetine administration prevents recurrence of pulmonary arterial hypertension and prolongs survival in rats.

1. The serotonin transporter (SERT) is strongly implicated in the pathogenesis of pulmonary arterial hypertension (PAH) in patients and animal models. Inhibitors of SERT have been reported to attenuate or reverse experimental PAH, which makes them potential therapeutic options for the treatment of PAH in humans. However, little is known about pathophysiological features after reversal or attenuation of PAH; moreover, the long-term therapeutic effects of SERT inhibitors on PAH remain undetermined. Thus, the aim of the present study was to investigate the short- and long-term effects of fluoxetine on monocrotaline (MCT)-induced PAH and associated pathophysiological changes in PAH models. 2. Rats were randomly divided into four groups as follows: (i) an M + F group, in which rats received a single injection of MCT (60 mg/kg, s.c.) and then after 3 weeks were given fluoxetine (10 mg/kg) once daily by gavage from Week 4 to Week 12; (ii) an M/F group, in which 3 weeks after a single MCT (60 mg/kg, s.c.) injection, rats were given fluoxetine (10 mg/kg) by daily gavage from Week 4 to Week 6 and were then given an equivalent volume of saline once daily by gavage from Week 7 to Week 12; (iii) an MCT group, in which 3 weeks after a single MCT (60 mg/kg, s.c.) injection rats were given an equivalent volume of saline by gavage from Week 4 to Week 12; and (iv) a saline group, in which rats received an equivalent volume of saline injection or gavage over the 12 week treatment period. Morphometric changes, pulmonary arterial pressure, percentage wall thickness, right ventricular hypertrophy index and SERT expression were detected at various times during the 12 week treatment period. Survival analysis was performed in each group. 3. After 12 weeks treatment, it was found that even through fluoxetine treatment resulted in complete reversal of PAH, PAH recurred after fluoxetine withdrawal. In contrast, continuous administration of fluoxetine prevented the recurrence of PAH and prolonged survival. Analysis of SERT protein levels in rat lung indicated that, compared with values obtained at Week 0, SERT protein increased significantly after discontinuation of fluoxetine but continuous fluoxetine administration inhibited this increase. 4. In conclusion, SERT overexpression correlates with the recurrence of PAH after withdrawal of fluoxetine in rats. Continuous fluoxetine administration prevents recurrence of PAH and prolongs survival.

Generation of strong quasistatic magnetic fields in interactions of ultraintense and short laser pulses with overdense plasma targets.

An analytical fluid model is proposed for the generation of strong quasistatic magnetic fields during normal incidence of a short ultraintense Gaussian laser pulse with a finite spot size on an overdense plasma. The steepening of the electron density profile in the originally homogeneous overdense plasma and the formation of electron cavitation as the electrons are pushed inward by the laser are included self-consistently. It is shown that the appearance of the cavitation plays an important role in the generation of quasistatic magnetic fields: the strong plasma inhomogeneities caused by the formation of the electron cavitation lead to the generation of a strong axial quasistatic magnetic field Bz. In the overdense regime, the generated quasistatic magnetic field increases with increasing laser intensity, while it decreases with increasing plasma density. It is also found that, in a moderately overdense plasma, highly intense laser pulses can generate magnetic fields approximately 100 MG and greater due to the transverse linear mode conversion process.

Long intergenic non-protein coding RNA 00858 functions as a competing endogenous RNA for miR-422a to facilitate the cell growth in non-small cell lung cancer.

The expression of long non-coding RNAs (lncRNAs) is dysregulated in non-small cell lung cancer (NSCLC). However, the functions and contributions of lncRNAs remain largely unknown. Here, we identified a critical role of long intergenic non-protein coding RNA 00858 (LINC00858) in NSCLC. Ectopic expression of LINC00858 in NSCLC cells promoted cell proliferation and induced cell migration and invasion. Moreover, LINC00858 functioned as a competitive endogenous RNA (ceRNA), effectively becoming sponge for miR-422a and thereby modulating the expression of kallikrein-related peptidase 4 (KLK4). In NSCLC patients, high expression of LINC00858 closely correlated with tumor progression. Thus, targeting the ceRNA network involving LINC00858 may be used as a treatment strategy against NSCLC.

Three Gorges Dam: Impact of Water Level Changes on the Density of Schistosome-Transmitting Snail Oncomelania hupensis in Dongting Lake Area, China.

BACKGROUND: Schistosomiasis remains an important public health issue in China and worldwide. Oncomelania hupensis is the unique intermediate host of schistosoma japonicum, and its change influences the distribution of S. japonica. The Three Gorges Dam (TGD) has substantially changed the ecology and environment in the Dongting Lake region. This study investigated the impact of water level and elevation on the survival and habitat of the snails. METHODS: Data were collected for 16 bottomlands around 4 hydrological stations, which included water, density of living snails (form the Anxiang Station for Schistosomiasis Control) and elevation (from Google Earth). Based on the elevation, sixteen bottomlands were divided into 3 groups. ARIMA models were built to predict the density of living snails in different elevation areas. RESULTS: Before closure of TGD, 7 out of 9 years had a water level beyond the warning level at least once at Anxiang hydrological station, compared with only 3 out of 10 years after closure of TGD. There were two severe droughts that happened in 2006 and 2011, with much fewer number of flooding per year compared with other study years. Overall, there was a correlation between water level changing and density of living snails variation in all the elevations areas. The density of living snails in all elevations areas was decreasing after the TGD was built. The relationship between number of flooding per year and the density of living snails was more pronounced in the medium and high elevation areas; the density of living snails kept decreasing from 2003 to 2014. In low elevation area however, the density of living snails decreased after 2003 first and turned to increase after 2011. Our ARIMA prediction models indicated that the snails would not disappear in the Dongting Lake region in the next 7 years. In the low elevation area, the density of living snails would increase slightly, and then stabilize after the year 2017. In the medium elevation region, the change of the density of living snails would be more obvious and would increase till the year 2020. In the high elevation area, the density of living snails would remain stable after the year 2015. CONCLUSION: The TGD influenced water levels and reduced the risk of flooding and the density of living snails in the study region. Based on our prediction models, the density of living snails in all elevations tends to be stabilized. Control of S. japonica would continue to be an important task in the study area in the coming decade.

[Effect of comprehensive schistosomiasis control measures with focus on buffalo and sheep removal in Anxiang County].

OBJECTIVE: To understand the effect of comprehensive schistosomiasis control measures with focus on buffalo and sheep removal in Anxiang City, Dongting Lake area. METHODS: The data of buffalo and sheep removal, routine schistosomiasis control measures such as disease detection and treatment, Oncomelania snail survey and control, as well as health education were collected and analyzed in Anxiang County, Hunan Province from 2004 to 2012. RESULTS: The schistosome infection rates of people, domestic animals and snails decreased from 11.23%, 17.06% and 1.07% in 2004 when the comprehensive measures had not been implemented to 0.58%, 0 and 0 in 2012, respectively. The average density of infected snails decreased from 0.003 4 snails/0.1 m2 to 0. CONCLUSION: The comprehensive control measures with focus on buffalo and sheep removal are significantly effective, and can control the transmission of schistosomiasis in marshland and lake regions.

[Evaluation of comprehensive measures with emphasis on schistosomiasis infectious source control at embankment level].

OBJECTIVE: To evaluate the effects of comprehensive measures with emphasis on schistosomiasis infectious source control at the embankment level. METHODS: The comprehensive measures with emphasis on schistosomiasis infectious source control were carried out, and the data of human and Oncomelania snail infection rates were collected and analyzed statistically at embankment levels. RESULTS: In Anbao Embankment, except the other comprehensive measures were performed, 2606 buffaloes were removed. The infection rates of residents reduced from 8.04% before the intervention to 0.7% after the intervention, and the infection rates of snails reduced from 0.56% to 0.05%. In Anli Embankment, 535 buffaloes were removed. In the third year after the intervention, the infection rates of residents reduced from 5.87% to 1.09%, and the infection rates of snails reduced from 0.17% to 0.07%. In Anzao Embankment, 62 buffaloes were removed. In the second year after the intervention, the infection rates of residents reduced from 2.67% to 0.39%, and the infection rates of snails reduced from 1.12% to 0.00%. In Anchang Embankment, the buffaloes were not removed. The human infection rates reduced from 1.76% before the intervention to 1.23% after the intervention. CONCLUSION: The comprehensive measures with emphasis on schistosomiasis infectious source control, especially the buffalo's removal, are effective in the control of schistosome infection rates of residents and snails.

[Short-term effect of black film covering on Oncomelania hupensis snail control in marshland and lake regions].

OBJECTIVE: To evaluate the short-term effect of the black film covering combined with niclosamide on Oncomelania hupensis snail control in marshland and lake regions. METHODS: A ditch with snails in Anxiang County was selected as the experimental sites. The ditch was divided into 3 groups: a film group, a niclosamide group, and a niclosamide and film group. The snails were surveyed before the test and 1, 3, 5, 7 days after the experiment. RESULTS: After the film covering, the highest temperature of the surface of soil was 63.7 degrees C on the first day, and the temperature higher than 40 degrees C lasted 4.34 hours. On the second day, the highest temperature was 52.3 degrees C, and the temperature higher than 40 degrees C lasted 4.96 hours. On the fourth day and fifth day, the temperature was lower than 30 degrees C, while the temperature was lower than 34 degrees C on the sixth day. On the seventh day of the experiment, the snail death rates of the film group, the niclosamide group, and the niclosamide and film group on the soil surface were 16.36%, 58.40% and 53.57%, respectively. On the seventh day, the snail death rates of the film group, and the niclosamide and film group under the soil were 20.00% and 40.00%, respectively, while no snails were found under the soil in the niclosamide group 3 days after the experiment. In mesh bags, the snail death rates of the film group, the niclosamide group, and the niclosamide and film group were 84.00%, 95.33% and 95.33%, respectively. CONCLUSION: The short-term effect of the black film covering on snail control is not obvious, and the black film covering does no promote the molluscicidal effect of niclosamide.

[Study on spatial distribution of advanced schistosomiasis at village level in Anxiang County based on geographic information system].

OBJECTIVE: To explore the spatial distribution and pattern of advanced schistosomiasis in Anxiang County so as to provide the evidence for improving advanced schistosomiasis control. METHODS: Based on the geographic database of advanced schistosomiasis distribution at the village level in Anxiang County, Hunan Province, the spatial autocorrelation analysis and spatial scan statistics were applied to analyze the spatial characteristics of distribution of advanced schistosomiasis. RESULTS: The global Moran's I of prevalence rate of advanced schistosomiasis was 0.06 (P > 0.05) and there was no spatial auto-correlation as a whole. The local spatial auto-correlation analysis showed that there were 9 villages with statistically significant LISA value (P < 0.05), among which existed high-high, low-high and high-low types of auto-correlation model. The results of SaTScan statistics was the same as local spatial auto-correlation analysis and showed the existence of one cluster area. CONCLUSIONS: There are local spatial auto-correlation and spatial aggregation of advanced schistosomiasis in Anxiang County. According to the distribution characteristics, we can assign resource more reasonably and control schistosomiasis more effectively.

[Application of multi-temporal China-Brazil Earth Recourses Satellite-02 data on surveillance of dynamic changes of water body of rivers and Oncomelania snail habitats in Anxiang County].

OBJECTIVE: To study the dynamic changes of the water body of rivers and Oncomelania snail habitats by using multi-temporal China-Brazil Earth Recourses Satellite-02 images taken in Anxiang County so as to establish the correct procedure for selecting images. METHODS: CBERS-02 images were collected on 20th December 2003, 10th February 2004, 10th April 2004, 19th June 2004, 10th August 2004 and 27th October 2004. Then the water body information from the study areas based on NDWI was extracted and the areas of water body were calculated to determine the images. RESULTS: The dynamic changes of the water body conformed to the rules of "water in summer and land in winter". Because of the rise of water, the water area in July was the biggest and the water area began to decline from August. The water area in April was the smallest. Then the wet season and the dry season should be June and April. CONCLUSION: The multi-temporal CBERS-02 images could be used to surveillance the dynamic changes of the water area and helpful in choosing the right images of the wet season and dry season.

[Study on spatial-temporal variation of infected snail in bottomland areas after an integrated control strategy at village level in the marshland and lake regions based on geographic information system].

OBJECTIVE: To evaluate the effect of an integrated control strategy and to quantify the spatial-temporal variation of infected snails in the bottomland areas after the strategy was implemented. METHODS: Based on the geographic database of infected snail distribution at the village level during 2004 - 2010 in Anxiang county, Hunan province, spatial autocorrelation analysis and spatial scan statistics were applied to analyze the spatial-temporal characteristics on the distribution of infected snails. RESULTS: The number of embankments with infected snails in Anxiang county decreased from 23 in 2004 to 10 in 2010, while the rate of frame with infected snail in embankments decreased from 4.32‰ in 2004 to 0.12‰ in 2010. The spatial distribution of infected snails was nonrandom, only in 2004 and 2005 with Moran's I = 0.21 (P < 0.10) and Moran's I = 0.13 (P < 0.10) respectively. Data from the local spatial auto-correlation analysis showed that the number of villages with H-H types of auto-correlation model had been gradually decreasing. The results of SaTScan statistics appeared the same as from the local spatial auto-correlation analysis, showing that the number of areas with increased risk was decreasing. CONCLUSION: The comprehensive measures with emphasis on infectious source control seemed effective for schistosomiasis control program. The current distribution characteristics provided us with evidence that the resource assignment could be more reasonably implemented so as to control schistosomiasis in a more effective way.

Magnetic-field generation and electron-collimation analysis for propagating fast electron beams in overdense plasmas.

An analytical fluid model is proposed for artificially collimating fast electron beams produced in the interaction of ultraintense laser pulses with specially engineered low-density-core-high-density-cladding structure targets. Since this theory clearly predicts the characteristics of the spontaneously generated magnetic field and its dependence on the plasma parameters of the targets transporting fast electrons, it is of substantial relevance to the target design for fast ignition. The theory also reveals that the rapid changing of the flow velocity of the background electrons in a transverse direction (perpendicular to the flow velocity) caused by the density jump dominates the generation of a spontaneous interface magnetic field for these kinds of targets. It is found that the spontaneously generated magnetic field reaches as high as 100 MG, which is large enough to collimate fast electron transport in overdense plasmas. This theory is also supported by numerical simulations performed using a two-dimensional particle-in-cell code. It is found that the simulation results agree well with the theoretical analysis.

[The clinical study on the adjunctive effects of aqueous extract from coptis root for the treatment of chronic periodontitis].

PURPOSE: To make a therapeutic membrane with aqueous extract from coptis root and explore its adjunctive effects for treating chronic periodontitis. METHODS: Drug membrane from coptis root aqueous extract was developed; 4 teeth in 30 patients with moderate to advanced periodontitis were randomly divided into four groups: coptis root membrane, iodine glycerin, single drug membrane and blank control group. All parameters including plaque index (PI), probing depth (PD), attachment loss (AL) and bleeding on probing (BOP) were measured at baseline, 4 and 7 weeks after treatment. Analysis of variance and chi-square test were carried out for analysis. RESULTS: In all four groups, there were significant differences of PD, AL, BOP between baseline and 4,7 weeks after treatment (P<0.05), the treatment effect of coptis root membrane was significantly superior to that of other three groups (P<0.05). Moreover, all the parameters improved continuously. CONCLUSION: Use of coptis root membrane as an adjunctive method after scaling can significantly improve the treatment effect of periodontitis.