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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease. Four major genes associated with ALS—SOD1, TARDBP, FUS, and C9orf72—have been identified, with the fused in sarcoma (FUS) gene demonstrating considerable genetic heterogeneity. Our research group has previously established an induced pluripotent stem (iPS) cell line harboring the c.1562G > A mutation in the FUS gene. The objective of this study is to create another iPS cell line featuring the pathogenic c.1126C > T mutation in the FUS gene. This research aims not only to establish a disease model for ALS linked to FUS mutations but also to pave the way for potential therapeutic interventions.

The Simplified Wet Bulb Globe Temperature (sWBGT) is widely used in heat stress assessments for climate-change studies, but its limitations have not been thoroughly explored. Building on recent critiques of sWBGT's use for current climate on global scale, this study examines sWBGT's biases using dynamically-downscaled sub-daily climate projections under multiple future emission scenarios. The analysis is aimed at understanding caveats in the application of sWBGT and the uncertainties in existing climate change analysis dependent on sWBGT. Results indicate sWBGT's biases are heavily influenced by local near-surface air temperature, with overestimation of heat stress in East Asia regions, particularly hot and humid areas, due to static assumptions of radiation and wind speed. This overestimation is amplified in warmer climates, leading to exaggerated projected heat stress increases in future. In contrast, underestimations are found for heat stress levels attributed to low wind speeds and strong radiations, such as over the Tibetan Plateau and certain extreme events. Additionally, sWBGT underestimates variability in extreme heatwave events compared to WBGT in both current and future climates, irrespective of overestimation in absolute heatwave intensities. This study emphasizes the limitations of sWBGT, especially in future warmer climates. Importance of sub-daily data for capturing daily maximum heat stress level and reflecting diurnal variations in different components is also discussed. In conclusion, we recommend using Liljegren's model (i.e., physics-based calculation) with high-resolution sub-daily climate data for more accurate outdoor heat stress assessments in climate change studies.

With global warming accelerating, the heavily populated and rapidly urbanized coastal regions of the Pearl River Delta (PRD) and the Yangtze River Delta (YRD) stand as representative areas with mounting concerns about extreme heat stress. This study analyzes differentiated effects of temperature (TAS) and relative humidity (RH) on human heat stress measured by wet-bulb globe temperature (WBGT) in those urban regions based on machine learning and mathematical derivation, while also examining the impacts of global warming and urbanization on prospective heat risks. To generate fine-scale climate projections targeted at the PRD and YRD, two global projections forced by Representative Concentration Pathway (RCP) 8.5 scenario are dynamically downscaled using non-hydrostatic Regional Climate Model version 4.7 (RegCM4), with the urban density and extent updated every year based on Shared Socioeconomic Pathways 5-8.5 (SSP5) scenario, thereby incorporating the transient urban growth into future projections. The bias-corrected downscaled simulations effectively capture the distinct interdependencies between TAS and RH on WBGT across different regions, similar to the observed patterns during the historical period. While the absolute contribution of TAS to WBGT is larger than RH regardless of warming levels and regions, the relative increase in RH becomes more pronounced with warming. Under RCP8.5 scenario, unprecedentedly extreme WBGT is projected to emerge in the far future (2080–2099). In contrast, the effect of urbanization appears to be more dominant in the near future (2030–2049) as urban density under SSP5 scenario is projected to peak around the 2040s and gradually decrease afterwards. The reduction of RH is found in the intensely urbanized areas locally, but it does not significantly lower WBGT because the positive contribution of increased TAS is more dominant. As a result, highly urbanized regions still exhibit higher WBGT compared to other areas. In addition, urban heat island effect is more pronounced for compact areas with high urban density (i.e., PRD) and at night. Despite the smaller temperature increase from urban heat island effect compared to global warming, it can play a critical role in exacerbating heat stress, adding to the already dangerous humid and hot conditions.

Vaccarin is a flavonoid glycoside, which has a variety of pharmacological properties and plays a protective role in diabetes and its complications, but its mechanism is unclear. In this study, we aim to investigate whether histone deacetylase 1(HDAC1), a gene that plays a pivotal role in regulating eukaryotic gene expression, is the target of miR-570-3p in diabetic vascular endothelium, and the potential molecular mechanism of vaccarin regulating endothelial inflammatory injury through miR-570-3p/HDAC1 pathway. The HFD and streptozotocin (STZ) induced diabetes mice model, a classical type 2 diabetic model, was established. The aorta of diabetic mice displayed a decrease of miR-570-3p, the elevation of HDAC1, and inflammatory injury, which were alleviated by vaccarin. Next, we employed the role of vaccarin in regulating endothelial cells miR-570-3p and HDAC1 under hyperglycemia conditions in vitro. We discovered that overexpression of HDAC1 counteracted the inhibitory effect of vaccarin on inflammatory injury in human umbilical vein endothelial cells (HUVECs). Manipulation of miRNA levels in HUVECs was achieved by transfecting cells with miR-570-3p mimic and inhibitor. Overexpression of miR-570-3p could decrease the expression of downstream components of HDAC1 including TNF-α, IL-1β, and malondialdehyde, while increasing GSH-Px activity in HUVECs under hyperglycemic conditions. Nevertheless, such phenomenon was completely reversed by miR-570-3p inhibitor, and administration of miR-570-3p inhibitor could block the inhibition of vaccarin on HDAC1 and inflammatory injury. Luciferase reporter assay confirmed the 3′- UTR of the HDAC1 gene was a direct target of miR-570-3p. In summary, our findings suggest that vaccarin alleviates endothelial inflammatory injury in diabetes by mediating miR-570-3p/HDAC1 pathway. Our study provides a new pathogenic link between deregulation of miRNA expression in the vascular endothelium of diabetes and inflammatory injury and provides new ideas, insights, and choices for the scope of application and medicinal value of vaccarin and some potential biomarkers or targets in diabetic endothelial dysfunction and vascular complications.

Abstract Background Mounting evidence suggested a complex correlation between host lipid metabolism and Toxoplasma gondii (T. gondii) infection. However, the inherent association between T. gondii infection and host lipid state remains elusive either in mice or in human hosts. Methods Through a study in a sample of 1045 healthy participants from eastern China, we determined the association of T. gondii infection and host lipid levels using serological methods. We then examined the host lipid levels in C57BL/6 J mice at both acute and chronic T. gondii infection stages (for a period up to 36 weeks post infection). Results In our case-control study, T. gondii seropositive individuals had higher low-density lipoproteins (LDL) (P = 0.0043) and total cholesterol (TC) (P = 0.0134) levels compared to seronegative individuals. Furthermore, individuals with LDL (OR = 3.25; 95% CI:1.60–6.61) and TC (OR = 2.10; 95% CI:1.22–3.63) levels above the upper limit of normal range had higher odds ratio to be T. gondii IgG positive. Consistently, in vivo data revealed that a significantly increased LDL level was first observed at early acute stage but plateaued to later time (chronic infection with T. gondii). Conclusions In both healthy population and T. gondii-infected mice, seropositive individuals had higher LDL level. Individuals with positive T. gondii IgG had more odds of being with LDL and TC abnormality. Latent T. gondii infection is common worldwide, potential medical interventions to host lipid metabolism may be a breakthrough point to the prevention and control of this parasite infection.

This study evaluates the performance of dynamical downscaling of global prediction generated from the NOAA Climate Forecast System (CFSv2) at subseasonal time-scale against dense in-situ observational data in Korea. The Weather Research and Forecasting (WRF) double-nested modeling system customized over Korea is adopted to produce very high resolution simulation that presumably better resolves geographically diverse climate features. Two ensemble members of CFSv2 starting with different initial conditions are downscaled for the summer season (June-July-August) during past 10-year (2011–2020). The comparison of simulations from the nested domain (5 km resolution) of WRF and driving CFSv2 (0.5°) clearly demonstrates the manner in which dynamical downscaling can drastically improve daily mean temperature (Tmean) and daily maximum temperature (Tmax) in both quantitative and qualitative aspects. The downscaled temperature not only better resolves the regional variability strongly tied with topographical elevation, but also substantially lowers the systematic cold bias seen in CFSv2. The added value from the nested domain over CFSv2 is far more evident in Tmax than in Tmean, which indicates a skillful performance in capturing the extreme events. Accordingly, downscaled results show a reasonable performance in simulating the plant heat stress index that counts the number of days with Tmax above 30°C and extreme degree days that accumulate temperature exceeding 30°C using hourly temperature. The WRF simulations also show the potential to capture the variation of Tmean-based index that represents the accumulation of heat stress in reproductive growth for the mid-late maturing rice cultivars in Korea. As the likelihood of extreme hot temperatures is projected to increase in Korea, the modeling skill to predict the ago-meteorological indices measuring the effect of extreme heat on crop could have significant implications for agriculture management practice.

Abstract Purpose To explore the potential role and unclear molecular mechanisms of vaccarin in wound healing. Methods Rats’ skin excision model to study the effects of vaccarin on wound healing in vivo . Hematoxylin and eosin staining was performed to evaluate Histopathologic characteristics. Immunohistochemistry was employed to assess the effects of vaccarin in accelerating angiogenesis. Western blot was used to evaluate relative protein expressed levels. Results Vaccarin could significantly promote wound healing and endothelial cells and fibroblasts proliferation in the wound site. Immunohistochemistry and Western blot studies showed that the nodal proteins and receptor (bFGFR) related to angiogenesis signaling pathway were activated, and the microvascular density in the wound site was markedly higher than that in the control group. Conclusions The present study was the first to demonstrate that vaccarin is able to induce angiogenesis and accelerate wound healing in vivo by increasing expressions of p-Akt, p-Erk and p-bFGFR. This process is mediated by MAPK/ERK and PI3K/AKT signaling pathways.

This study investigates the performance of the latest version of RegCM4 in simulating summer precipitation over South Korea, comparing nine sensitivity experiments with different combinations of convective parameterization schemes (CPSs) between land and ocean. In addition to the gross pattern of seasonal and monthly mean precipitation, the northward propagation of the intense precipitation band and statistics from extreme daily precipitation are thoroughly evaluated against gridded and in situ station observations. The comparative analysis of 10-year simulations demonstrates that no CPS shows superiority in both quantitative and qualitative aspects. Furthermore, a nontrivial discrepancy among the different observation datasets makes a robust assessment of model performance difficult. Regardless of the CPS over the ocean, the simulations with the Kain–Fritsch scheme over land show a severe dry bias, whereas the simulations with the Tiedtke scheme over land suffer from a limited accuracy in reproducing spatial distributions due to the excessive orographic precipitation. In general, the simulations with the Emanuel scheme over land are better at capturing the major characteristics of summer precipitation over South Korea, despite not all statistical metrics showing the best performance. When applying the Emanuel scheme to both land and the ocean, precipitation tends to be slightly overestimated. This deficiency can be alleviated by using either the Tiedtke or Kain–Fritsch schemes over the ocean instead. As few studies have applied and evaluated the Tiedtke and Kain–Fritsch schemes to the Korean region within the RegCM framework, and this study introduces the potential of these new CPSs compared with the more frequently selected Emanuel scheme, which is particularly beneficial to RegCM users.

Chronic wound repair is a common complication in patients with diabetes mellitus, which causes a heavy burden on social medical resources and the economy. Hypaphorine (HYP) has good anti-inflammatory effect, and chitosan (CS) is used in the treatment of wounds because of its good antibacterial effect. The purpose of this research was to investigate the role and mechanism of HYP-nano-microspheres in the treatment of wounds for diabetic rats. The morphology of HYP-NPS was observed by transmission electron microscopy (TEM). RAW 264.7 macrophages were used to assess the bio-compatibility of HYP-NPS. A full-thickness dermal wound in a diabetic rat model was performed to evaluate the wound healing function of HYP-NPS. The results revealed that HYP-NPS nanoparticles were spherical with an average diameter of approximately 50 nm. The cell experiments hinted that HYP-NPS had the potential as a trauma material. The wound test in diabetic rats indicated that HYP-NPS fostered the healing of chronic wounds. The mechanism was through down-regulating the expression of pro-inflammatory cytokines IL-1β and TNF-α in the skin of the wound, and accelerating the transition of chronic wound from inflammation to tissue regeneration. These results indicate that HYP-NPS has a good application prospect in the treatment of chronic wounds.

Background /Aims: Accumulating evidence indicates that endothelial inflammation is one of the critical determinants in pathogenesis of atherosclerotic cardiovascular disease. Our previous studies had demonstrated that Vaccariae prevented high glucose or oxidative stress-triggered endothelial dysfunction in vitro. Very little is known about the potential effects of hypaphorine from Vaccariae seed on inflammatory response in endothelial cells. Methods: In the present study, we evaluated the anti-inflammatory effects of Vaccariae hypaphorine (VH) on lipopolysaccharide (LPS)-challenged endothelial EA.hy926 cells. The inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), monocyte chemoattractant protein 1 (MCP-1) and vascular cellular adhesion molecule-1 (VCAM-1) were measured by real-time PCR (RT-PCR). The expressions of adenosine monophosphate-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), toll-like receptor 4 (TLR4), peroxisome proliferator-activated receptor γ (PPARγ) were detected by Western blotting or immunofluorescence. Results: We showed that LPS stimulated the expressions of TNF-α, IL-1β, MCP-1, VCAM-1 and TLR4, but attenuated the phosphorylation of AMPK and ACC as well as PPARγ protein levels, which were reversed by VH pretreatment. Moreover, we observed that LPS-upregulated TLR4 protein expressions were inhibited by PPARγ agonist pioglitazone, and the downregulated PPARγ expressions in response to LPS were partially restored by knockdown of TLR4. The negative regulation loop between TLR4 and PPARγ response to LPS was modulated by AMPK agonist AICAR (5-Aminoimidazole-4-carboxamide riboside or acadesine) or A769662. Conclusions: Taken together, our results suggested that VH ameliorated LPS-induced inflammatory cytokines production in endothelial cells via inhibition of TLR4 and activation of PPARγ, dependent on AMPK signalling pathway.

This study evaluates the resolution dependency of scaling precipitation with temperature from the perspective of the added value of high-resolution (5 km) dynamical downscaling using various kinds of long-term climate change projections over South Korea. Three Coupled Model Intercomparison Project Phase 5 (global climate models (GCMs) with different climate sensitivities, and one pseudo global warming (PGW) experiment, are downscaled by Weather Research and Forecasting one-way double nested modeling system with convective parameterization for the reference (1976–2005) and future (2071–2100) periods under RCP8.5 scenario. A detailed comparison of the driving GCM/PGW, 20 km mother simulation, and 5 km nested simulation demonstrates improved representation of precipitation with increasing resolution not only in the spatial pattern and magnitude for both the mean and the extremes, but also in a more realistic representation of extreme precipitation’s sensitivities to temperature. According to the projected precipitation changes downscaled from both GCM ensemble and PGW, there will be intensified precipitation, particularly for the extremes, over South Korea under the warming, which is primarily contributed by convective precipitation increase that shows higher temperature sensitivity. This study also compares the extreme precipitation-temperature scaling relations within-epoch (apparent scaling) and between-epoch (climate scaling). It confirms that the magnitude and spatial pattern of the two scaling rates can be quite different, and the precipitation change over Korea under global warming is mainly controlled by thermodynamic factors.

This study examines the changes in the intensity and frequency of precipitation in China from a multi‐model perspective on 20 statistically downscaled fine-scale climate projections and categorizes them into four distinct patterns in response to globally targeted warming (1.5 °C and 3 °C). In a multivariate setting, the asymmetric responses of frequency and intensity to different levels of warming can be considered jointly. This study focuses on relatively moderate precipitation to determine if the ensemble of a subset of climate models, which are selected based on the categorization, can provide a better interpretation of the changing patterns compared to that from the conventional unweighted ensemble mean. The results show that the spatial distribution of the predominant category and inter-model agreement are dependent mainly on the degree of warming. As warming becomes more extensive, the projected change in precipitation tends to converge to the category that indicates an increase in both the intensity and frequency of precipitation, from the mixed-mode and even decreasing pattern. The use of subsampling to produce an ensemble of joint probability (or return period) has potential benefits in detecting asymmetric changes in the intensity and frequency of precipitation that is seen in the majority of models but hidden by the unweighted ensemble average particularly for regions where different models show mixed signals. A substantial portion of the region in China is likely to experience a transition of changes in precipitation frequency and (or) intensity under continuous warming, which would not be revealed clearly by univariate analysis.

This study describes the chemical constituents of Albiziae Cortex and their ability to ameliorate steatosis and promote proliferation and anti-oxidation in vitro. Together, five known lignan glycosides, (7S,8R)-erythro-syringylglycerol-β−O-4′-sinapyl ether 9-O-β-D-glucopyranoside (1), (+)-lyoniresinol-9′-O-gluco-side (2), (−)-lyoniresinol-9′-O-glucoside (3), picraquassioside C (4), and icariside E5 (5), were isolated from the Albiziae Cortex. Their structures were elucidated by extensive NMR and high-resolution mass spectrometry analysis and compared with reported data. Oil Red O staining results revealed that compounds 1, 2, and 3 attenuated lipid accumulation and lipid metabolic disorders in FFAs (oleate/palmitate, 2:1 ratio, 0.3 mM)-exposed HepG2 cells. The Cell Counting Kit 8 (CCK-8) assay results revealed that compounds 1 and 5 can significantly promote human umbilical vein endothelial cell (HUVEC) proliferation; meanwhile, these compounds did not exhibit significant cytotoxicity against HUVECs. In addition, 2′,7′-dichlorofluorescein diacetate (DCFH-DA) staining results revealed that high glucose (HG)-induced reactive oxygen species (ROS) production was abolished by compounds 1, 2, and 3. This is the first report of the isolation of lignan skeletons from the genus Albizzia julibrissin with the ability to ameliorate steatosis and promote proliferation and anti-oxidation activities.

The bamboo shoot of Pleioblastus amarus (Keng) Keng f. is a medicinal and edible plant product in China. In this study, the chemical composition of the total alkaloids from bamboo shoots and bamboo shoot shells of P. amarus (Keng) Keng f. (ABSP and ABSSP, respectively) were separated and investigated by UHPLC/QTOF-MS/MS. The results showed that a total of 32 alkaloids were extracted, with 15 common to both ABSP and ABSSP and 10 and 7 alkaloids distinct to ABSP and ABSSP, respectively. ABSP and ABSSP both decreased the lipopolysaccharide (LPS, 0.5 μg/mL)-induced nitric oxide (NO) production in RAW264.7 murine macrophages with half maximal inhibitory concentration (IC50) values of 78 and 55 μg/mL, respectively. We also found that ABSP and ABSSP (100 μg/mL) could decrease the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at both mRNA and protein levels in LPS-exposed RAW264.7 cells. Moreover, 100 μg/mL of ABSP and ABSSP also significantly inhibited LPS-induced mRNA expression of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α). Additionally, ABSP and ABSSP (100 μg/mL) decreased the phosphorylation of extracellular regulated protein kinase (ERK) in LPS-stimulated RAW264.7 cells. Collectively, the total alkaloids from the bamboo shoots and shells of P. amarus exhibit anti-inflammatory effects in LPS-activated RAW264.7 cells through the inhibition of ERK signaling. This result can provide support for the medicinal use and further study of P. amarus.

[Objectives] To investigate the mechanisms and pharmacologic effects of Citri Reticulatae Pericarpium against keloids by network pharmacology systematically. [Methods] TCMSP, Uniprot and BATMAN-TCM databases were used to obtain the active constituents and targets of Citri Reticulatae Pericarpium. "Keloid" was used as key word to search for related therapeutic targets from Drug Bank, OMIM, TTD, and GEO databases. The Chinese medicine compound-target network was constructed by Cytoscape software. Besides, gene ontology (GO) and Kyoto Encyclopedia of genes and genome enrichment analysis were also performed. Afterward, Discovery Studio software was used to assess the interaction of key components and genes. [Results] Five active components of Citri Reticulatae Pericarpium, 773 compound targets and 676 keloid treatment targets were obtained in the databases. After the intersection, there are 47 targets of Citri Reticulatae Pericarpium for treating keloids. Hub genes were identified such as MMP9, IL6, TNF, TP53, and VEGFA, which were enriched in tumor necrosis factor-α, nuclear factor kappa-B, and other signaling pathways. The molecular docking stimulation confirmed the interaction between the MMP9 and three components of Citri Reticulatae Pericarpium. [Conclusions] Citri Reticulatae Pericarpium may play an important role in treating keloids through modulating genes and signaling pathways. The present study sheds light on the mechanisms of active compounds of Citri Reticulatae Pericarpium for the treatment of keloids. [ABSTRACT FROM AUTHOR]

This paper reviewed the shortcomings of conventional therapies for ischemic stroke and discussed the methods of vascular regenera- tion, stem cell differentiation, homing and neuronal remodeling after ischemic stroke, to provide potential therapeutic ideas for ischemic stroke. [ABSTRACT FROM AUTHOR]

Statistical bias correction (BC) is a widely used tool to post-process climate model biases for heat-stress impact studies, which are often based on indices calculated from multiple dependent variables. This study compares five bias correction methods (four univariate and one multivariate) with two applying strategies (direct and indirect) for correcting two heat-stress indices with different dependencies on temperature and relative humidity, using multiple Regional Climate Model simulations over South Korea. It would be helpful for reducing the ambiguity involved in the practical application of BC for climate modeling as well as end-user communities. Our results demonstrate that the multivariate approach can improve the corrected inter-variable dependence and therefore benefit the indirect correction of heat-stress indices that depend on the adjustment of individual components, especially those relying equally on multiple drivers. On the other hand, the direct correction of multivariate indices using the Quantile Delta Mapping univariate approach can also produce a comparable performance in the corrected heat-stress indices. However, our results also indicate that attention should be paid to the nonstationarity of bias brought by climate sensitivity in the modeled data, which may affect the bias-corrected results unsystematically. Careful interpretation of the correction process is required for an accurate heat-stress impact assessment. [ABSTRACT FROM AUTHOR]

Oxidized low-density lipoprotein (ox-LDL) accumulation is one of the critical determinants in endothelial dysfunction in many cardiovascular diseases such as atherosclerosis. C1q/TNF-related protein 9 (CTRP9) is identified to be an adipocytokine with cardioprotective properties. However, the potential roles of CTRP9 in endothelial function remain largely elusive. In the present study, the effects of CTRP9 on the proliferation, apoptosis, migration, angiogenesis, nitric oxide (NO) production and oxidative stress in human umbilical vein endothelial cells (HUVECs) exposed to ox-LDL were investigated. We observed that treatment with ox-LDL inhibited the proliferation, migration, angiogenesis and the generation of NO, while stimulated the apoptosis and reactive oxygen species (ROS) production in HUVECs. Incubation of HUVECs with CTRP9 rescued ox-LDL-induced endothelial injury. CTRP9 treatment reversed ox-LDL-evoked decreases in antioxidant enzymes including heme oxygenase-1 (HO-1), nicotinamide adenine dinucleotide phosphate (NAD(P)H) dehydrogenase quinone 1, and glutamate-cysteine ligase (GCL), as well as endothelial nitric oxide synthase (eNOS). Furthermore, CTRP9 induced activation of peroxisome proliferator-activated receptor γ co-activator 1α (PGC1-α) and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK). Of interest, AMPK inhibition or PGC1-α silencing abolished CTRP9-mediated antioxidant enzymes levels, eNOS expressions, and endothelial protective effects. Collectively, we provided the first evidence that CTRP9 attenuated ox-LDL-induced endothelial injury by antioxidant enzyme inductions dependent on PGC-1α/AMPK activation. [ABSTRACT FROM AUTHOR]

Abstract Endothelial lesion response to injurious stimuli is a necessary step for initiating inflammatory cascades in blood vessels. Hypaphorine (Hy) from different marine sources is shown to exhibit anti-inflammatory properties. However, the potential roles and possible molecular mechanisms of Hy in endothelial inflammation have yet to be fully clarified. We showed that Hy significantly inhibited the positive effects of lipopolysaccharide (LPS) on pro-inflammatory cytokines expressions, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), monocyte chemoattractant protein 1 (MCP-1) and vascular cellular adhesion molecule-1 (VCAM-1), as well as induction of the phosphorylation of Akt and mTOR in HMEC-1 cells. The downregulated peroxisome proliferator-activated receptor γ (PPAR-γ) and upregulated toll-like receptor 4 (TLR4) expressions in LPS-challenged endothelial cells were prevented by Hy. Inhibition of both PI3K and mTOR reversed LPS-stimulated increases in TLR4 expressions and decreases in PPAR-γ levels. Genetic silencing of TLR4 or PPAR-γ agonist pioglitazone obviously abrogated the levels of pro-inflammatory cytokines in LPS-treated HMEC-1 cells. These results suggest that Hy may exert anti-inflammatory actions through the regulation of TLR4 and PPAR-γ dependent on PI3K/Akt/mTOR signal pathways. Hy may be considered as a therapeutic agent that can potentially relieve or ameliorate endothelial inflammation-associated diseases. [ABSTRACT FROM AUTHOR]

Background: Activation of macrophage is involved in many inflammation diseases. Lipopolysaccharide (LPS) is a powerful inflammatory signal contributing to monocytes/macrophages activation associated with increased proinflammatory cytokines expressions. We recently identified that vaccarin was expected to protect endothelial cells from injury. Hypaphorine was abundantly found in vaccaria semen. However, the potential roles and underlying mechanisms of vaccaria hypaphorine on macrophage inflammation have been poorly defined. Methods: This study was designed to determine the effects of vaccaria hypaphorine on LPS-mediated inflammation in RAW 264.7 cells. Results: In this study, we demonstrated that vaccaria hypaphorine dramatically ameliorated LPS-induced nitric oxide (NO) release and productions of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, monocyte chemoattractant protein 1 (MCP-1) and prostaglandin E2 (PGE2) in RAW 264.7 cells. LPS-stimulated expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were down-regulated by vaccaria hypaphorine. Furthermore, vaccaria hypaphorine retarded LPS-induced phosphorylation of ERK, nuclear factor kappa beta (NFκB), NFκB inhibitor IκBα, and IKKβ. Immunofluorescence staining revealed that vaccaria hypaphorine eliminated the nuclear translocation of NFκB in LPS-treated RAW 264.7 cells. Conclusion: It was seen that vaccaria hypaphorine counteracted inflammation via inhibition of ERK or/and NF?B signaling pathways. Collectively, we concluded that vaccaria hypaphorine can be served as an anti-inflammatory candidate. [ABSTRACT FROM AUTHOR]

Endothelial cell injury is a critical component of atherosclerosis and hypertension. Vaccarin is considered to be of potential benefit in the treatment of vascular diseases. The aim of the present study was to evaluate the possible effects of vaccarin in human EA•hy926 cells induced by high glucose, and to investigate its underlying mechanism in the prevention and treatment of high glucose-induced injury. In the present study, EA•hy926 cells were exposed to 90, 180 and 270 mM high glucose for 24 h, and the induced cell injury was examined using a sulforhodamine B assay. Following treatment with high glucose, it was found that high glucose stimulated cell injury, resulting in reduced cell viability and migratory ability, increased lactate dehydrogenase (LDH) leakage and malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) activity. High glucose further accelerated cell apoptosis via activating Notch1 and Hairy and enhancer of split 1. It was found that preincubation with vaccarin protected the EA•hy926 cells from high glucose-induced cell injury, which promoted cell viability and migratory ability, inhibited the expression levels of LDH and MDA, and enhanced the activity of SOD. Cell migratory ability, LDH leakage, MDA levels and decreasing SOD activity were evaluated using a wound healing assay and corresponding assay kits. Cell apoptosis was detected by flow cytometry with an Annexin V-fluorescein isothiocyanate/propidium iodide apoptosis detection kit and Hoechst staining. Furthermore, western blotting was used to detect the protein expression levels of Notch1, Hes1 and caspase-3. In particular, in addition to inducing the downregulation of Notch signaling, vaccarin treatment downregulated the cell apoptotic pathway-associated protein caspase 3. These findings suggested that vaccarin may be able to selectively protect the vascular endothelium from dysfunction induced by high glucose. [ABSTRACT FROM AUTHOR]

Reservoirs play an important role in modifying the natural hydrological regime. Reservoir-induced changes in flow fluctuations at monthly and hourly scales were analyzed through a case study of a tributary of the Yangtze River (China), the Qingyi River, where the Chencun reservoir is located at the upper reaches. Monthly and hourly flow data were collected from two flow gauging stations monitoring the inflow and outflow regimes, respectively. The flow fluctuations were characterized by coefficient of variation (CV) and concentration degree (Cd). Continuous Morlet wavelet transform was applied to detect diurnal period. The influence of the reservoir was revealed comparing the postdam with the predam conditions by and comparing the affected with the natural conditions. The results indicate two opposite change patterns. Reservoir impoundment may mitigate flow fluctuations at both of the monthly and the hourly scales. At a monthly scale, reservoirs usually impound water in the flood season for the dry season. At an hourly scale, reservoirs may restrain a flood pulse and strictly control the outflow. Thus, the reservoirs reduce variation and concentration of the runoff distribution within a year and within a day. In contrast, the reservoirs may aggravate the hourly flow fluctuation by releasing hydropeaking waves for hydropower generation and superimpose a diurnal period to the downstream flow regime. But the artificial diurnal fluctuation is of some uncertainty in terms of appearance time and duration. This work may deepen the understanding of the reservoirs influence mechanism on the downstream flow regime. [ABSTRACT FROM AUTHOR]

Angiogenesis is a major pathological component of several diseases, including traumatic vascular disease and coronary heart disease. The purpose of the present study was to determine the effects of vaccarin on endothelial cell migration and neovascularization, which are important and necessary components of wound healing. The present study investigated and confirmed neovascularization induced by vaccarin in vitro and in vivo. In vitro, the effects of vaccarin (1.08 and 2.15 µM) on proliferation, migration and tube formation of human microvascular endothelial cells (HMEC)-1 were evaluated via sulforhodamine B assay and migration and tube formation assay, respectively. Furthermore, a mouse Matrigel plus model was used to detect capillary-like tube structures in vivo. Immunohistochemistry was used to detect the protein expression of cluster of differentiation 31 (CD31), p-AKT and p-extracellular-signal-regulated kinases (Erk). Vaccarin significantly promoted HMEC-1 proliferation and migration and tube formation of HMEC-1 at a dose of 2.15 μM. In vivo, vaccarin delivered by daily oral administration significantly improved epidermal growth factor-induced angiogenesis in an intradermal inoculation mouse model. The mouse Matrigel model study also revealed that vaccarin significantly promoted neovascularization via detection of CD31 levels and enhanced protein expression of p-Akt and p-Erk. In addition, vaccarin also promoted expression of CD31. [ABSTRACT FROM AUTHOR]

Dried stem bark from Albizia julibrissin (AJ) is a highly valued Traditional Chinese Medicine, which has been shown to suppress tumor growth and angiogenesis. Total saponins from AJ (TSAJ) are one of the most bioactive components of AJ extract. The present study evaluated the anti-tumor and anti-angiogenic effects of TSAJ in vitro and in vivo. The anti-angiogenic activity of TSAJ was investigated by measuring the effects on vascular endothelial growth factor (VEGF)-induced proliferation, migration and tube formation of Ea.hy926 endothelial cells in vitro. The expression levels of proteins associated with VEGF-induced angiogenesis were determined by western blotting. Furthermore, in vivo Matrigel™ plug and H22 hepatoma tumor models were used to verify the anti-angiogenic effects of TSAJ. The present study demonstrated that TSAJ significantly inhibited VEGF-mediated endothelial cell proliferation, migration and tube formation of Ea.hy926 cells in vitro. The anti-angiogenic effects of TSAJ were modulated by suppression of phosphorylated-(p-) focal adhesion kinase, p-Akt, and p-extracellular signal-regulated kinase in the VEGF/VEGF receptor 2 (R2) signaling pathway. Furthermore, oral administration of TSAJ significantly inhibited tumor growth and tumor-induced angiogenesis, as well as the formation of functional vessels, in the Matrigel™ plug model. These results suggest that TSAJ may be a potentialpotential anti-angiogenic agent that targets the VEGF/VEGFR2 signaling pathway, and inhibits tumor-induced angiogenesis. [ABSTRACT FROM AUTHOR]

Summary The copolymers of polysiloxane and acrylate with methacryloxypropyl trimethoxysilane (MPS) –polydimethylsiloxane (PDMS) oligomer as macromonomer and Gemini surfactant as co-emulsifier were prepared by emulsion copolymerization and characterized by 1HNMR, Gel-permeation chromatography (GPC), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and FT-IR. Firstly, the oligomers of MPS-PDMS with different Si-O-Si chain length (8, 12, 24 and 36) were synthesized by the hydrolysis of MPS and the ring-opening polymerization of octamethyl tetracyclosiloxane (D4), the 1HNMR and FT-IR spectra indicated that when the reaction time was prolonged to 2 h, more than 90% of -Si (OCH3)3 groups were hydrolyzed; Then, the emulsion polymerization was carried out with the oligomer as macromonomer and Gemini Surfactant as co-emulsifier. XPS investigation of the latexes showed that with the increase of Si-O-Si chain length, more and more polysiloxane occupied the outer layer of membrane, which agreed well with the conclusion of contact angle and AFM measurements. With Gemini surfactant as co-emulsifier in the system, the PDMS content in the system could reach 50%, which was far higher than the other reported value. [ABSTRACT FROM AUTHOR]