Gastrodin Attenuates Colitis and Prevents Tumorigenesis in Mice by Interrupting TLR4/MD2/NF-κB Signaling Transduction.

INTRODUCTION: Chronic inflammation is one of the causative factors for tumorigenesis. Gastrodin is a main active ingredient isolated from Gastrodia elata Blume, a famous medicinal herb with a long edible history. AIM: This study aimed to explore the effects of gastrodin on colitis-associated carcinogenesis (CRC) in mice and to elucidate its potential molecular mechanisms. METHODS: Balb/c mice were induced with azoxymethane (AOM) and dextran sulfate sodium (DSS) for 12 weeks. Gastrodin (50 mg/kg) was administered via oral gavage three times per week until the end of the experiment. Disease indexes, including body weight, bloody diarrhea, colon length, histopathological score, and tumor size, were measured. Tumor cell proliferation was evaluated by BrdU incorporation assay and tumor cell cytotoxicity was assessed by cell counting kit (CCK-8). The expression levels of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling molecules, NF-κB luciferase, and pro-inflammatory cytokines were determined by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), immunoblotting, immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA), or reporter gene assays. The binding affinity between gastrodin and myeloid differentiation protein-2 (MD2) was analyzed by molecular docking and cellular thermal shift assay (CETSA). RESULTS: Gastrodin administration was demonstrated to mitigate various CRC-related symptoms in mice, including weight loss, diarrhea, and tissue abnormalities. Notably, gastrodin suppressed tumor cell growth during colitis- associated tumorigenesis, resulting in fewer and smaller adenomas in the colon. Unlike irinotecan, a broadspectrum antitumor drug, gastrodin did not exhibit apparent cytotoxicity in various colorectal adenocarcinoma cell lines. Additionally, gastrodin downregulated TLR4/NF-κB signaling molecules and pro-inflammatory mediators in mice and macrophages. Molecular docking and CETSA experiments suggested that gastrodin binds to the MD2 protein, potentially interfering with the recognition of lipopolysaccharide (LPS) by TLR4, leading to NF-κB pathway inhibition. CONCLUSION: This study provides evidence for the first time that gastrodin attenuated colitis and prevented colitisrelated carcinogenesis in mice, at least partially, by diminishing tumor-promoting cytokines through the interruption of TLR4/MD2/NF-κB signaling transduction.

Nuciferine alleviates collagen-induced arthritic in rats by inhibiting the proliferation and invasion of human arthritis-derived fibroblast-like synoviocytes and rectifying Th17/Treg imbalance.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder marked by persistent synovial inflammation and joint degradation, posing challenges in the development of effective treatments. Nuciferine, an alkaloid found in lotus leaf, has shown promising anti-inflammatory and anti-tumor effects, yet its efficacy in RA treatment remains unexplored. This study investigated the antiproliferative effects of nuciferine on the MH7A cell line, a human RA-derived fibroblast-like synoviocyte, revealing its ability to inhibit cell proliferation, promote apoptosis, induce apoptosis, and cause G1/S phase arrest. Additionally, nuciferine significantly reduced the migration and invasion capabilities of MH7A cells. The therapeutic potential of nuciferine was further evaluated in a collagen-induced arthritis (CIA) rat model, where it markedly alleviated joint swelling, synovial hyperplasia, cartilage injury, and inflammatory infiltration. Nuciferine also improved collagen-induced bone erosion, decreased pro-inflammatory cytokines and serum immunoglobulins (IgG, IgG1, IgG2a), and restored the balance between T helper (Th) 17 and regulatory T cells in the spleen of CIA rats. These results indicate that nuciferine may offer therapeutic advantages for RA by decreasing the proliferation and invasiveness of FLS cells and correcting the Th17/Treg cell imbalance in CIA rats.

A generic approach to construct pseudo components for oil weathering models.

Oil weathering models are essential for predicting the behavior of spilled oil in the environment. Most models use a "Pseudo Component" (PC) approach to represent the wide range of compounds found in petroleum products. Within the approach, rather than modeling each individual compound in an oil, a manageable number of PCs are developed that represent whole classes of compounds. However, previous studies focused mainly on traditional crude oils and did not develop a generic approach to create an optimal set of PCs for a variety of oils. In developing the updates to the NOAA oil weathering model, we propose herein a generic approach to construct PCs using oil distillation data to capture the complexity of oil evaporative weathering. We validated our approach with 899 oils from the Automated Data Inquiry for Oil Spills (ADIOS) oil library and found that an optimal set of sixteen PCs should be used. These PCs include two with low boiling point (below 144 °C), one with a high boiling point (above 400 °C), and thirteen constructed within a middle range of boiling points with a temperature resolution of 20 °C. Our simulation tests suggested that this set of sixteen PCs adequately characterizes oil evaporation processes for a wide variety of oils.

Numerical simulation of multiphase oil behaviors in ice-covered nearshore water.

There has been an increase in marine transportation in cold regions, which in turn has led to an increasing risk of oil spills in these areas. To better support risk assessment and pollution control of oil spills, it is important to have a good understanding of oil transport in the environment. This information is essential to manage response priorities and help prepare contingency and mitigating measures. This study aims to simulate 3D wave propagation in shallow water with different broken-ice aerial coverage percentages to assess the fate and transport of oil spill in a nearshore area under different conditions. Based on the Reynolds-averaged Navier-Stokes momentum equations for an incompressible viscous fluid and the Volume of Fluid (VOF) method that is coupled with Six Degree of Freedom (6-DOF) model, a 3D numerical model of three-phase transient flow was developed. It was found that the presence of ice makes the spreading of spilled oil slower in the horizontal direction since the ice can build natural barriers to oil movement. The higher the ice concentration, the slower spilled oil migrates in all directions. The maximum oil volume fraction varies with increasing ice coverage on the water surface area. The wave frequency, the averaged flow velocity, and oil properties affect the oil spread extent and the oil volume fraction. The dumping effect of the wave due to the presence of ice makes the impact of this factor less critical than those in open water.

Oil biodegradation in permeable marine sediments: Effects of benthic pore-water advection and solute exchange.

Oil spills have been recognized as among the worst kinds of environmental disasters, causing severe coastal ecological and economic damages. Although benthic flow and solute fluxes are known to have strong impacts on fate and transport of oil deposited within marine sediments, their endogenous mechanisms still remain to be uncovered. In this paper, simulations of flow and solute transport processes along with hydrocarbon biodegradation were conducted in a cylindrical benthic chamber system to investigate influences of benthic hydrodynamics on oil biodegradation in permeable marine sediments. Results show that ripple-flow interactions create subsurface recirculation cells whereby seawater infiltrates into the benthic sediments at ripple troughs while groundwater discharges near the crests. It results in a spatially varied oil biodegradation rate in marine sediments. Significant oil biodegradation occurs near sediment ripple troughs due to direct oxygen recharge, while biodegradation of oil deposited uphill becomes slow due to limited oxygen replenishment. Oil biodegradation decreases subsurface oxygen content, and consequently impedes discharge of oxygen from benthic sediments. Our results reveal a dynamic interaction between oil biodegradation and benthic flow and solute transport processes, which has strong implications for predicting oil persistence and biodegradation within marine sediments and its associated impacts on benthic biogeochemical processes.

Berberine Improves Irinotecan-Induced Intestinal Mucositis Without Impairing the Anti-colorectal Cancer Efficacy of Irinotecan by Inhibiting Bacterial ß-glucuronidase.

Irinotecan (CPT11), a broad-spectrum cytotoxic anticancer agent, induces a series of toxic side-effects. The most conspicuous side-effect is gastrointestinal mucositis, including nausea, vomiting, and diarrhea. A growing body of evidence indicates that bacteria ß-glucuronidase (GUS), an enzyme expressed by intestinal microbiota, converts the inactive CPT11 metabolite SN38G to the active metabolite SN38 to ultimately induce intestinal mucositis. We sought to explore the potential efficacy and underlying mechanisms of berberine on CPT11-induced mucositis. Our study showed that berberine (50 mg/kg; i. g.) mitigated the CPT11-induced loss of mucosal architecture, ulceration, and neutrophil infiltration. Meanwhile, berberine improved mucosal barrier function by increasing the number of globlet cells, protecting trans-endothelial electrical resistance (TEER), reducing permeability and increasing tight junction proteins expression. LC-MS analysis showed that berberine decreased the content of SN38 in feces, which correlated with decreases in both GUS activity and GUS-producing bacteria. Further molecular docking and Lineweaver-Burk plots analyses suggested that berberine functions as a potential non-competitive inhibitor against GUS enzyme. Of note, berberine maintained the anti-tumor efficacy of CPT11 in a tumor xenograft model while abrogating the intestinal toxicity of CPT11. Overall, we identified for the first time the remission effects of berberine on intestinal mucositis induced by CPT11 without impairing the anti-colorectal cancer efficacy of CPT11 partially via inhibiting bacterial GUS enzyme.

Hypersaline Pore Water in Gulf of Mexico Beaches Prevented Efficient Biodegradation of Deepwater Horizon Beached Oil.

The 2010 Deepwater Horizon (DWH) blowout released 3.19 million barrels (435 000 tons) of crude oil into the Gulf of Mexico. Driven by currents and wind, an estimated 22 000 tons of spilled oil were deposited onto the northeastern Gulf shorelines, adversely impacting the ecosystems and economies of the Gulf coast regions. In this work we present field work conducted at the Gulf beaches in three U.S. States during 2010-2011: Louisiana, Alabama, and Florida, to explore endogenous mechanisms that control persistence and biodegradation of the MC252-oil deposited within beach sediments as deep as 50 cm. The work involved over 1500 measurements incorporating oil chemistry, hydrocarbon-degrading microbial populations, nutrient and DO concentrations, and intrinsic beach properties. We found that intrinsic beach capillarity along with groundwater depth provides primary controls on aeration and infiltration of near-surface sediments, thereby modulating moisture and redox conditions within the oil-contaminated zone. In addition, atmosphere-ocean-groundwater interactions created hypersaline sediment environments near the beach surface at all the studied sites. The fact that the oil-contaminated sediments retained near or above 20% moisture content and were also eutrophic and aerobic suggests that the limiting factor for oil biodegradation is the hypersaline environment due to evaporation, a fact not reported in prior studies. These results highlight the importance of beach porewater hydrodynamics in generating unique hypersaline sediment environments that inhibited oil decomposition along the Gulf shorelines following DWH.

Multiphase CFD simulation of the nearshore spilled oil behaviors.

Oil spills are a serious environmental problem. To better support risk assessment and pollution control for oil spills, a good understanding of oil transport in the environment is required. This study focused on the numerical simulation of the nearshore oil behaviors based on computational fluid dynamics. Based on the Navier-Stokes momentum equations for an incompressible viscous fluid and volume of fluid (VOF) method, a 3D numerical model of three-phase transient flow was developed. The wave number, averaged flow velocity and oil properties would affect the oil spread extent and the oil volume fraction. The higher the averaged flow velocity and wave number, the lower the oil concentration, and the faster the horizontal movement of the oil. The spilled oil may move to contact the seafloor by increasing the averaged flow velocity at the inlet boundary. Through increasing the wave number, the oil would stay near the water surface. In the nearshore, where the wave is the main seawater motion, the oil containment boom should be set preferentially to the direction of wave transmission for oil cleaning. This study shows that by doubling the wave number and increasing the averaged flow velocity (ten times) at the same time, the maximum oil volume fraction would be reduced by around 32%. Finally, the water temperature had no significant impact on the oil migration, and the impact of evaporation should be considered in the simulation.

Bioremediation of the Exxon Valdez oil in Prince William Sound beaches.

Oil from the Exxon Valdez laden with polycyclic aromatic hydrocarbons (PAH) has persisted on some beaches in Prince William Sound, Alaska, >20years after these beaches became contaminated. The degradation rate of the total PAH (TPAH) is estimated at 1% per year. Low oxygen concentrations were found to be the major factor causing oil persistence, and bioremediation through the injection of hydrogen peroxide and nutrients deep into four beaches in PWS were conducted in the summers of 2011 and 2012. It was found that due to the treatment, the TPAH biodegradation rate was between 13% and 70% during summer 2011 and summer 2012. The results also showed high efficiency in the delivery of oxygen and nutrient to the contaminated areas of the beach. However, the approach has an environmental cost associated with it, and stakeholders would need to conduct a rigorous net environmental benefit analysis (NEBA) for pursuing the bioremediation of submerged contaminated sediments, especially in higher latitudes.

A-DROP: A predictive model for the formation of oil particle aggregates (OPAs).

Oil-particle interactions play a major role in removal of free oil from the water column. We present a new conceptual-numerical model, A-DROP, to predict oil amount trapped in oil-particle aggregates. A new conceptual formulation of oil-particle coagulation efficiency is introduced to account for the effects of oil stabilization by particles, particle hydrophobicity, and oil-particle size ratio on OPA formation. A-DROP was able to closely reproduce the oil trapping efficiency reported in experimental studies. The model was then used to simulate the OPA formation in a typical nearshore environment. Modeling results indicate that the increase of particle concentration in the swash zone would speed up the oil-particle interaction process; but the oil amount trapped in OPAs did not correspond to the increase of particle concentration. The developed A-DROP model could become an important tool in understanding the natural removal of oil and developing oil spill countermeasures by means of oil-particle aggregation.

Oil droplets transport due to irregular waves: Development of large-scale spreading coefficients.

The movement of oil droplets due to waves and buoyancy was investigated by assuming an irregular sea state following a JONSWAP spectrum and four buoyancy values. A technique known as Wheeler stretching was used to model the movement of particles under the moving water surface. In each simulation, 500 particles were released and were tracked for a real time of 4.0 h. A Monte Carlo approach was used to obtain ensemble properties. It was found that small eddy diffusivities that decrease rapidly with depth generated the largest horizontal spreading of the plume. It was also found that large eddy diffusivities that decrease slowly with depth generated the smallest horizontal spreading coefficient of the plume. The increase in buoyancy resulted in a decrease in the horizontal spreading coefficient, which suggests that two-dimensional (horizontal) models that predict the transport of surface oil could be overestimating the spreading of oil.

Simulation of the landfall of the Deepwater Horizon oil on the shorelines of the Gulf of Mexico.

We conducted simulations of oil transport from the footprint of the Macondo Well on the water surface throughout the Gulf of Mexico, including deposition on the shorelines. We used the U.S. National Oceanic Atmospheric Administration (NOAA) model General NOAA Operational Modeling Environment (GNOME) and the same parameter values and input adopted by NOAA following the Deepwater Horizon (DWH) blowout. We found that the disappearance rate of oil off the water surface was most likely around 20% per day based on satellite-based observations of the disappearance rate of oil detected on the sea surface after the DWH wellhead was capped. The simulations and oil mass estimates suggest that the mass of oil that reached the shorelines was between 10,000 and 30,000 tons, with an expected value of 22,000 tons. More than 90% of the oil deposition occurred on the Louisiana shorelines, and it occurred in two batches. Simulations revealed that capping the well after 2 weeks would have resulted in only 30% of the total oil depositing on the shorelines, while capping after 3 weeks would have resulted in 60% deposition. Additional delay in capping after 3 weeks would have averted little additional shoreline oiling over the ensuing 4 weeks.