Byakangelicol suppresses TiPs-stimulated osteoclastogenesis and bone destruction via COX-2/NF-κB signaling pathway.

Aseptic loosening (AL) is considered a significant cause of prosthesis revision after arthroplasty and a crucial factor in the longevity of an artificial joint prosthesis. The development of AL is primarily attributed to a series of biological reactions, such as peri-prosthetic osteolysis (PPO) induced by wear particles around the prosthesis. Chronic inflammation of the peri-prosthetic border tissue and hyperactivation of osteoclasts are key factors in this process, which are induced by metallic wear particles like Ti particles (TiPs). In our in vitro study, we observed that TiPs significantly enhanced the expression of inflammation-related genes, including COX-2, IL-1ß and IL-6. Through screening a traditional Chinese medicine database, we identified byakangelicol, a traditional Chinese medicine molecule that targets COX-2. Our results demonstrated that byakangelicol effectively inhibited TiPs-stimulated osteoclast activation. Mechanistically, we found that byakangelicol suppressed the expression of COX-2 and related pro-inflammatory factors by modulating macrophage polarization status and NF-κB signaling pathway. The in vivo results also demonstrated that byakangelicol effectively inhibited the expression of inflammation-related factors, thereby significantly alleviating TiPs-induced cranial osteolysis. These findings suggested that byakangelicol could potentially be a promising therapeutic approach for preventing PPO.

Evolving therapeutic landscape of advanced hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common solid malignancies worldwide. A large proportion of patients with HCC are diagnosed at advanced stages and are only amenable to systemic therapies. We have witnessed the evolution of systemic therapies from single-agent targeted therapy (sorafenib and lenvatinib) to the combination of a checkpoint inhibitor plus targeted therapy (atezolizumab plus bevacizumab therapy). Despite remarkable advances, only a small subset of patients can obtain durable clinical benefit, and therefore substantial therapeutic challenges remain. In the past few years, emerging systemic therapies, including new molecular-targeted monotherapies (for example, donafenib), new immuno-oncology monotherapies (for example, durvalumab) and new combination therapies (for example, durvalumab plus tremelimumab), have shown encouraging results in clinical trials. In addition, many novel therapeutic approaches with the potential to offer improved treatment effects in patients with advanced HCC, such as sequential combination targeted therapy and next-generation adoptive cell therapy, have also been proposed and developed. In this Review, we summarize the latest clinical advances in the treatment of advanced HCC and discuss future perspectives that might inform the development of more effective therapeutics for advanced HCC.

Chemical Composition and Thermogravimetric Behaviors of Glanded and Glandless Cottonseed Kernels.

Common "glanded" (Gd) cottonseeds contain the toxic compound gossypol that restricts human consumption of the derived products. The "glandless" (Gl) cottonseeds of a new cotton variety, in contrast, show a trace gossypol content, indicating the great potential of cottonseed for agro-food applications. This work comparatively evaluated the chemical composition and thermogravimetric behaviors of the two types of cottonseed kernels. In contrast to the high gossypol content (3.75 g kg-1) observed in Gd kernels, the gossypol level detected in Gl kernels was only 0.06 g kg-1, meeting the FDA's criteria as human food. While the gossypol gland dots in Gd kernels were visually observed, scanning electron microcopy was not able to distinguish the microstructural difference between ground Gd and Gl samples. Chemical analysis and Fourier transform infrared (FTIR) spectroscopy showed that Gl kernels and Gd kernels had similar chemical components and mineral contents, but the former was slightly higher in protein, starch, and phosphorus contents. Thermogravimetric (TG) processes of both kernels and their residues after hexane and ethanol extraction were based on three stages of drying, de-volatilization, and char formation. TG-FTIR analysis revealed apparent spectral differences between Gd and Gl samples, as well as between raw and extracted cottonseed kernel samples, indicating that some components in Gd kernels were more susceptible to thermal decomposition than Gl kernels. The TG and TG-FTIR observations suggested that the Gl kernels could be heat treated (e.g., frying and roasting) at an optimal temperature of 140-150 °C for food applications. On the other hand, optimal pyrolysis temperatures would be much higher (350-500 °C) for Gd cottonseed and its defatted residues for non-food bio-oil and biochar production. The findings from this research enhance the potential utilization of Gd and Gl cottonseed kernels for food applications.

NIR light-controlled mitochondria-targeted delivery of carbon monoxide combined with histone deacetylase inhibition for synergistic anticancer therapy.

A multifunctional nanoplatform APIPB-MnCO@TPP@N,P-GQDs (APIPB = N-(2-aminophen-yl)-4-(1H-imidazo[4,5-f] [1, 10] phenanthrolin-2-yl) benzamide, TPP = triphenylphosphine, Mn = manganese, CO = carbon monoxide, and GQDs = graphene quantum dots), nanoplatform (1), was synthesized, which consists of a fluorescent N, P-doped GQDs carrier with its surface covalently functionalized by an CO donor APIPB-MnCO with histone deacetylases (HDAC) inhibitory property and a TPP derivative directing group. Nanoplatform (1) selectively localized in the mitochondria of HeLa cells to inhibit HDAC activity, and released CO upon 808 nm near-infrared light irradiation, destroying the mitochondria and thus inducing cancer cells apoptosis. The targeted subcellular mitochondrial CO delivery combined with inhibitory HDAC activity maximized the cytotoxicity of the nanoplatform which may provide new insights for CO-mediated multimodal therapies for cancer treatment.

Long read sequencing of Toona sinensis (A. Juss) Roem: A chromosome-level reference genome for the family Meliaceae.

Chinese mahogany (Toona sinensis) is a woody plant that is widely cultivated in China and Malaysia. Toona sinensis is important economically, including as a nutritious food source, as material for traditional Chinese medicine and as a high-quality hardwood. However, the absence of a reference genome has hindered in-depth molecular and evolutionary studies of this plant. In this study, we report a high-quality T. sinensis genome assembly, with scaffolds anchored to 28 chromosomes and a total assembled length of 596 Mb (contig N50 = 1.5 Mb and scaffold N50 = 21.5 Mb). A total of 34,345 genes were predicted in the genome after homology-based and de novo annotation analyses. Evolutionary analysis showed that the genomes of T. sinensis and Populus trichocarpa diverged ~99.1-103.1 million years ago, and the T. sinensis genome underwent a recent genome-wide duplication event at ~7.8 million years and one more ancient whole genome duplication event at ~71.5 million years. These results provide a high-quality chromosome-level reference genome for T. sinensis and confirm its evolutionary position at the genomic level. Such information will offer genomic resources to study the molecular mechanism of terpenoid biosynthesis and the formation of flavour compounds, which will further facilitate its molecular breeding. As the first chromosome-level genome assembled in the family Meliaceae, it will provide unique insights into the evolution of members of the Meliaceae.

Drug discovery and formulation development for acute pancreatitis.

Acute pancreatitis is a sudden inflammation and only last for a short time, but might lead to a life-threatening emergency. Traditional drug therapy is an essential supportive method for acute pancreatitis treatment, yet, failed to achieve satisfactory therapeutic outcomes. To date, it is still challenging to develop therapeutic medicine to redress the intricate microenvironment promptly in the inflamed pancreas, and more importantly, avoid multi-organ failure. The understanding of the acute pancreatitis, including the causes, mechanism, and severity judgment, could help the scientists bring up more effective intervention and treatment strategies. New formulation approaches have been investigated to precisely deliver therapeutics to inflammatory lesions in the pancreas, and some even could directly attenuate the pancreatic damages. In this review, we will briefly introduce the involved pathogenesis and underlying mechanisms of acute pancreatitis, as well as the traditional Chinese medicine and the new drug option. Most of all, we will summarize the drug delivery strategies to reduce inflammation and potentially prevent the further development of pancreatitis, with an emphasis on the bifunctional nanoparticles that act as both drug delivery carriers and therapeutics.

Effect of Cr(III) Adsorption on the Dissolution of Boehmite Nanoparticles in Caustic Solution.

The incorporation of relatively minor impurity metals onto metal (oxy)hydroxides can strongly impact solubility. In complex highly alkaline multicomponent radioactive tank wastes such as those at the Hanford Nuclear Reservation, tests indicate that the surface area-normalized dissolution rate of boehmite (γ-AlOOH) nanomaterials is at least an order of magnitude lower than that predicted for the pure phase. Here, we examine the dissolution kinetics of boehmite coated by adsorbed Cr(III), which adheres at saturation coverages as sparse chemisorbed monolayer clusters. Using 40 nm boehmite nanoplates as a model system, temperature-dependent dissolution rates of pure versus Cr(III)-adsorbed boehmite showed that the initial rate for the latter is consistently several times lower, with an apparent activation energy 16 kJ·mol-1 higher. Although the surface coverage is only around 50%, solution analysis coupled to multimethod solids characterization reveal a phyicochemical armoring effect by adsorbed Cr(III) that substantially reduces the number of dissolution-active sites on particle surfaces. Such findings could help improve kinetics models of boehmite and/or metal ion adsorbed boehmite nanomaterials, ultimately providing a stronger foundation for the development of more robust complex radioactive liquid waste processing strategies.

Feasibility of using biochar as buffer and mineral nutrients replacement for acetone-butanol-ethanol production from non-detoxified switchgrass hydrolysate.

Biochar can be an inexpensive pH buffer and source of mineral and trace metal nutrients in acetone-butanol-ethanol (ABE) fermentation. This study evaluated the feasibility of replacing expensive 4-morpholineethanesulfonic acid (MES) P2 buffer and mineral nutrients with biochar made from switchgrass (SGBC), forage sorghum (FSBC), redcedar (RCBC) and poultry litter (PLBC) for ABE fermentation. Fermentations using Clostridium beijerinckii ATCC 51743 in glucose and non-detoxified switchgrass hydrolysate media were performed at 35 °C in 250 mL bottles for 72 h. Medium containing buffer and minerals without biochar was the control. Similar ABE production (about 18.0 g/L) in glucose media with SGBC, FSBC and RCBC and control was measured. However in non-detoxified switchgrass hydrolysate medium, SGBC, RCBC and PLBC produced more ABE (about 18.5 g/L) than the control (10.1 g/L). This demonstrates that biochar is an effective buffer and mineral supplement for ABE production from lignocellulosic biomass without costly detoxification process.

Cr(III) Adsorption by Cluster Formation on Boehmite Nanoplates in Highly Alkaline Solution.

The development of advanced functional nanomaterials for selective adsorption in complex chemical environments requires partner studies of binding mechanisms. Motivated by observations of selective Cr(III) adsorption on boehmite nanoplates (γ-AlOOH) in highly caustic multicomponent solutions of nuclear tank waste, here we unravel the adsorption mechanism in molecular detail. We examined Cr(III) adsorption to synthetic boehmite nanoplates in sodium hydroxide solutions up to 3 M, using a combination of X-ray diffraction (XRD), Raman, X-ray photoelectron spectroscopy (XPS), scanning/transmission electron microscopy (S/TEM), electron energy loss spectroscopy (EELS), high-resolution atomic force microscopy (HR-AFM), time-of-fight secondary ion mass spectrometry (ToF-SIMS), Cr K-edge X-ray absorption near edge structure (XANES)/extended X-ray absorption fine structure (EXAFS), and electron paramagnetic resonance (EPR). Adsorption isotherms and kinetics were successfully fit to Langmuir and pseudo-second-order kinetic models, respectively, consistent with monotonic uptake of Cr(OH)4- monomers until saturation coverage of approximately half the aluminum surface site density. High resolution AFM revealed monolayer cluster self-assembly on the (010) basal surfaces with increasing Cr(III) loading, possessing a structural motif similar to guyanaite (ß-CrOOH), stabilized by corner-sharing Cr-O-Cr bonds and attached to the surface with edge-sharing Cr-O-Al bonds. The selective uptake appears related to short-range surface templating effects, with bridging metal connections likely enabled by hydroxyl anion ligand exchange reactions at the surface. Such a cluster formation mechanism, which stops short of more laterally extensive heteroepitaxy, could be a metal uptake discrimination mechanism more prevalent than currently recognized.

Tetrandrine, a novel inhibitor of ether-à-go-go-1 (Eag1), targeted to cervical cancer development.

Mortality-to-incidence ratios in patients with cancer are extremely high, positioning cancer as a major cause of death worldwide. Ether-à-go-go-1 (Eag1) is an ion channel that plays important roles in tumour proliferation, malignant transformation, invasion, metastasis, recurrence, and prognosis. Therefore, identifying potent and specific Eag1 channel inhibitors is crucial. In this study, we identified the first natural inhibitor of Eag1, the traditional Chinese medicine agent tetrandrine, and explored the underlying mechanism. Tetrandrine directly interacted with Eag1 and inhibited the currents in a concentration-dependent manner (IC50 of 69.97 ± 5.2 µM), and the amino acids Ile 550 , Thr 552 , and Gln 557 in the Eag1 C-linker domain were critical for tetrandrine's inhibitory effect. Moreover, tetrandrine reduced the proliferation of HeLa cells and Chinese hamster ovary (CHO) cells stably expressing Eag1 in a concentration-dependent manner. Finally, tetrandrine (30 mg/kg/day) inhibited tumor growth in mice, demonstrating a 64.21% inhibitory rate of HeLa cell-transplanted tumors. These results suggest that tetrandrine is a potent and selective Eag1 channel inhibitor, and could act as a leading compound in the development of therapies for Eag1 ion channel dysfunction-induced diseases.

CD8+ T cells mediate the antitumor activity of frankincense and myrrh in hepatocellular carcinoma.

BACKGROUND: Tumor-promoting inflammation is an emerging hallmark of cancer, which participates in both cancer progression and immune escape. Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer with an extremely poor prognosis. Frankincense and myrrh are anti-inflammation agents commonly used in clinic. The purpose of this study is to investigate whether extract of frankincense and myrrh (FM) downregulates inflammatory microenvironment of HCC and thereby restores antitumor immune responses. METHODS: The water-decocting FM was obtained and quantified. HCC cell lines HCCLM3 and Hepa1-6 were used to evaluate the efficacy of FM targeting NF-κB and STAT3 signaling with western blot and qRT-PCR analysis. CD8+NKG2D+ cells were derived from human peripheral blood and were used for evaluation of immune cells-mediated inflammation and oncolysis on HCCLM3 cells. The antitumor efficacy of FM was investigated both in immune compromised and immune competent mice bearing subcutaneous HCC. Mice received daily oral gavage of FM at 60 mg/kg. Immune activity within tumor microenvironment (TME) was assessed by ELISpot assay and flow cytometry, respectively. Depletion of CD8+ T cells or NK cells was achieved by intraperitoneal injection of respective neutralizing antibody. RESULTS: FM significantly inhibited the activation of NF-κB and STAT3 signaling in HCC cells induced by cytokines (TNF-α or IL-6) and in co-culture system with CD8+NKG2D+ cells. Furthermore, FM sensitized HCC cells to CD8+NKG2D+ cells-mediated oncolysis. In HCC-bearing mice, FM at a non-toxic dose failed to reduce tumor growth in immune compromised mice, whereas it significantly inhibited tumor growth and prolonged life span in immune competent mice. While the number of IFN-γ-producing cells within TME was increased in mice treated with FM, the infiltration of CD8+ T cells and NK cells was not increased. Finally, we identified that depletion of CD8+ T cells rather than NK cells abrogated the antitumor activity of FM. CONCLUSIONS: Our results show for the first time that CD8+ T cells mediate the antitumor activity of FM at a non-toxic dose. This may provide new insights to this ancient mysterious prescription in cancer therapy, which offers a novel and practical therapeutic strategy and the possibilities of combined immunotherapy for HCC as well as other inflammation-related cancers in clinic.

Xianyu decoction attenuates the inflammatory response of human lung bronchial epithelial cell.

BACKGROUND: Xianyu decoction (XD), a Chinese experience recipe, shows inhibitory effects on lung cancer. However, the potential functions of XD on pneumonia were unknown. This study aimed to investigate the effect of XD on inflammatory response of childhood pneumonia. METHODS: Human lung bronchial epithelial cell line BEAS-2B was cultured in different doses of LPS with or without XD treatment. The expression of miR-15a and IKBKB were altered by transfection assay. RT-PCR and western blot were used to evaluate the effects of XD and miR-15a mimic/inhibitor on the expression levels of miR-15a, IKBKB, p65 and IκBα. ELISA was used to determine the levels of CRP, IL-6 and IL-8. RESULTS: High expression of miR-15a was observed in serum and cell model of pneumonia. miR-15a promoted the expression of inflammatory cytokines IL-6, IL-8, CRP and IKBKB in vitro. XD treatment downregulated the level of miR-15a in pneumonia children. In addition, XD reduced the expression of inflammatory cytokines and the phosphorylation levels of p65 and IκBα by inhibition of miR-15a and IKBKB expression in LPS-stimulated BEAS-2B cells. CONCLUSION: XD downregulated the level of miR-15a in serum of pneumonia children. Additionally, XD inhibited inflammatory response in LPS-stimulated BEAS-2B cells possibly by blocking IKBKB/NF-κB signal pathway which was regulated by miR-15a.

A systematic data acquisition and mining strategy for chemical profiling of Aster tataricus rhizoma (Ziwan) by UHPLC-Q-TOF-MS and the corresponding anti-depressive activity screening.

In this study, a systematic data acquisition and mining strategy aimed at the traditional Chinese medicine (TCM) complex system based on ultra high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UHPLC-Q-TOF-MS) was reported. The workflow of this strategy is as follows: First, the high resolution mass data are acquired by both data-dependent acquisition mode (DDA) and data-independent acquisition mode (DIA). Then a global data mining that combined targeted and non-targeted compound finding is applied to analyze mass spectral data. Furthermore, some assistant tools, such as key product ions (KPIs), are employed for compound hunting and identification. The TCM Ziwan (ZW, Aster tataricus rhizoma) was used to illustrate this strategy for the first time. In this research, total 131 compounds including organic acids, peptides, terpenes, steroids, flavonoids, coumarins, anthraquinones and aldehydes were identified or tentatively characterized in ZW based on accurate mass measurements within ±5 ppm error, and 50 of them were unambiguously confirmed by comparing standard compounds. Afterwards, based on the traditional Chinese medical theory and the key determinants of firing patterns of ventral tegmental area (VTA) dopamine (DA) neurons in the development of depression, the confirmed compounds were subsequently evaluated the pharmacological effect of activity of VTA DA neurons and anti-depressive efficacy. This research provided not only a chemical profiling for further in vivo study of ZW, but also an efficient data acquisition and mining strategy to profile the chemical constituents and find new bioactive substances for other TCM complex system.

Mindfulness and asthma symptoms: A study among college students.

INTRODUCTION: Given the known link between asthma and stress as well as the link between mindfulness and stress, we explore the possible association between trait mindfulness and asthma-related diagnosis and symptoms with a cross-sectional study. METHOD: In 2014, we surveyed a sample of college students in their freshman year, from a public university in Shanghai, China. We used three multilevel logistic regressions to estimate the association between trait mindfulness (measured by Mindful Awareness Attention Scale, MAAS) and self-report of ever having an asthma diagnosis, ever having had persistent dry cough, and ever having had wheezing symptoms. Age, gender, household registration status, and the frequency of smog in the respondent's hometown were used as control variables in the study. The home province of the student was used as the cluster variable in the multilevel models. RESULTS: Among the 1392 students in the analysis sample (mean age = 18.3), 47 (3.4%) self-reported an asthma diagnosis, 251 (18.1%) reported having had persistent dry cough, and 100 (7.2%) reported having had wheezing symptoms. A one-unit increase in MAAS is negatively associated with having a self-reported asthma diagnosis (Odds Ratio (OR): 0.662, 95% Confidence Interval (CI): 0.452, 0.969, p = 0.034), having had persistent dry cough (OR: 0.658, 95% CI: 0.545, 0.795, p < 0.001), and wheezing (OR = 0.747, 95% CI: 0.569, 0.981, p = 0.036). DISCUSSION: This is the first study to suggest a link between trait mindfulness and asthma. Our finding provides evidence that people with higher level of mindfulness are less likely to have had an asthma diagnosis and less likely to have the symptoms of persistent dry cough and wheezing.

Identification of Resveratrol, an Herbal Compound, as an Activator of the Calcium-Activated Chloride Channel, TMEM16A.

Calcium-activated chloride channels (CaCCs) play vital roles in a variety of physiological processes. Dysfunction of the CaCCs is implicated in many diseases. Drug discovery targeting at CaCCs has recently become possible with the determination that TMEM16A is the molecular identity of CaCCs. In this study, we demonstrated that resveratrol (RES), a Chinese traditional medicine compound, is a novel activator of TMEM16A. The yellow fluorescence protein quenching assay and measurement of intracellular calcium fluorescence intensity show that RES activates TMEM16A channels in an intracellular Ca2+-independent way. The data of inside-out patch clamp revealed that RES dose-dependently activates TMEM16A (EC50 = 47.92 ± 9.35 µM). Furthermore, RES enhanced the contractions of the ileum of guinea pigs by activating the TMEM16A channel, which indicated that RES might be a promising drug for the treatment of gastrointestinal hypomotility. As RES was able to induce TMEM16A channel activation, TMEM16A can be added to the list of RES drug targets.

Cavidine Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via NF-κB Signaling Pathway in vivo and in vitro.

Acute lung injury (ALI) is characterized by widespread inflammation in the lungs and alveolar-capillary destruction, causing high morbidity and mortality. Cavidine, isolated from Corydalis impatiens, have been exhibited to have potent anti-inflammatory effects in previous studies. The purpose of this study was to evaluate the protective effect of cavidine on lipopolysaccharide (LPS)-induced ALI and to enunciate the underlying in vivo and in vitro mechanisms. Mice were intraperitoneally administrated with cavidine (1, 3, or 10 mg/kg) at 1 and 12 h, prior to the induction of ALI by intranasal administration of LPS (30 mg/kg). Blood samples, lung tissues, and bronchoalveolar lavage fluid (BALF) were harvested after LPS challenge. Furthermore, we used LPS-induced lung epithelial cells A549 to examine the mechanism of cavidine to lung injury. The results showed that pretreatment with cavidine significantly decreased lung wet-to-dry weight (W/D) ratio, reduced pro-inflammatory cytokine levels including TNF-α and IL-6 in BALF and serum from LPS-stimulated mice, and attenuated lung histopathological changes. In addition, western blot results showed that cavidine inhibited the phosphorylation of nuclear factor-kappaB (NF-κB) p65 and IκBα induced by LPS. In conclusion, our results demonstrate that cavidine protects against LPS-induced acute lung injury in mice via inhibiting of pro-inflammatory cytokine TNF-α and IL-6 production and NF-κB signaling pathway activation. Taken together, cavidine may be useful for the prevention and treatment of pulmonary inflammatory diseases, such as ALI.

Ginsenoside Rb1, a novel activator of the TMEM16A chloride channel, augments the contraction of guinea pig ileum.

Calcium-activated chloride channels (CaCCs) play important roles in many physiological processes, and the molecular basis of CaCCs has been identified as TMEM16A in many cell types. It is well established that TMEM16A is a drug target in many diseases, including cystic fibrosis, hypertension, asthma, and various tumors. Therefore, identifying potent and specific modulators of the TMEM16A channel is crucial. In this study, we identified the first natural activator of TMEM16A from traditional Chinese medicine and explored its mechanism. Our data showed that Ginsenoside Rb1 (GRb1) can activate TMEM16A directly from the intracellular side in a dose-dependent manner at an EC50 of 38.4 ± 2.14 µM. GRb1 specifically activated TMEM16A/B, but not the other previously proposed CaCC mediators such as CFTR and bestrophin. Moreover, GRb1 promoted proliferation of CHO cells stably expressing TMEM16A, in a concentration-dependent manner. Finally, we showed that GRb1 increased the amplitude and frequency of contractions in an isolated guinea pig ileum assay in vivo. In summary, GRb1 can be considered a lead compound for the development of novel drugs for the treatment of diseases caused by TMEM16A dysfunction.

Structural characterization and immunomodulatory activity of a new polysaccharide from jellyfish.

A new polysaccharide (JSP-11) with a molecular weight of 1.25×106Da was extracted and purified from jellyfish. Monosaccharide analysis showed that JSP-11 was composed of mannose, galactose and glucuronic acid with a molar ratio of 2.18:1.00:1.94. According to the analysis of fourier transform-infrared spectroscopy, methylation analysis, and NMR spectroscopy, JSP-11 was determined to contain a linear backbone which consisted of (1→3,6)-linked ß-d-Manp and (1→6)-linked ß-d-Galp. The branch of (1→)-linked α-d-GlcpA was attached to the C-3 position of (1→3,6)-linked ß-d-Manp in the backbone. The immunomodulatory assay exhibited that JSP-11 could significantly enhance the viability of RAW 264.7 macrophage cells, and promote the release of NO, TNF-α, and IL-1ß via activating NF-κB, MAPKs and PI3K/Akt signal pathways.

Southern Phosphorus Indices, Water Quality Data, and Modeling (APEX, APLE, and TBET) Results: A Comparison.

Phosphorus (P) Indices in the southern United States frequently produce different recommendations for similar conditions. We compared risk ratings from 12 southern states (Alabama, Arkansas, Florida, Georgia, Kentucky, Louisiana, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, and Texas) using data collected from benchmark sites in the South (Arkansas, Georgia, Mississippi, North Carolina, Oklahoma, and Texas). Phosphorus Index ratings were developed using both measured erosion losses from each benchmark site and Revised Universal Soil Loss Equation 2 predictions; mostly, there was no difference in P Index outcome. The derived loss ratings were then compared with measured P loads at the benchmark sites by using equivalent USDA-NRCS P Index ratings and three water quality models (Annual P Loss Estimator [APLE], Agricultural Policy Environmental eXtender [APEX], and Texas Best Management Practice Evaluation Tool [TBET]). Phosphorus indices were finally compared against each other using USDA-NRCS loss ratings model estimate correspondence with USDA-NRCS loss ratings. Correspondence was 61% for APEX, 48% for APLE, and 52% for TBET, with overall P index correspondence at 55%. Additive P Indices (Alabama and Texas) had the lowest USDA-NRCS loss rating correspondence (31%), while the multiplicative (Arkansas, Florida, Louisiana, Mississippi, South Carolina, and Tennessee) and component (Georgia, Kentucky, and North Carolina) indices had similar USDA-NRCS loss rating correspondence-60 and 64%, respectively. Analysis using Kendall's modified Tau suggested that correlations between measured and calculated P-loss ratings were similar or better for most P Indices than the models.

Anti-ulcerogenic effect of cavidine against ethanol-induced acute gastric ulcer in mice and possible underlying mechanism.

Cavidine, a major alkaloid compound isolated from Corydalis impatiens, has various pharmacological effects but its effect on gastric ulcer has not been previously explored. The current study aimed to investigate the possible anti-ulcerogenic potential of cavidine in the model of ethanol-induced gastric ulcer. Mice received cavidine (1, 5 or 10mg/kg, ig), cimetidine (CMD, 100mg/kg, ig) or vehicle at 12h and 1h before absolute ethanol administration (0.5mL/100g), and animals were euthanized 3h after ethanol ingestion. Gross and histological gastric lesions, biochemical, immunological and Western blot parameters were taken into consideration. The results showed that ethanol administration produced apparent mucosal injuries with morphological and histological damage, whereas cavidine pre-treatment reduced the gastric injuries. Cavidine pre-treatment also ameliorated the contents of malonaldehyde (MDA) and myeloperoxidase (MPO) activity, and increased the mucosa levels of glutathione (GSH), superoxide dismutase (SOD) and prostaglandin E2 (PGE2), relative to the model group. Also cavidine was able to decrease the levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), inhibit the up-regulation of cyclo-oxygenase-2 (COX-2) expression and activation of Nuclear factor-kappa B (NF-κB) pathway. Taken together, these results indicated that cavidine exerts a gastroprotective effect against gastric ulceration, and the underlying mechanism might be associated with the stimulation of PGE2, reduction of oxidative stress, suppression of NF-κB expression and subsequent reduced COX-2 and pro-inflammatory cytokines.