Study on the Mechanism of Yadanzi Oil in Treating Lung Cancer Based on Network Pharmacology and Molecular Docking Technology.

Brucea javanica oil emulsion (BJOE) is a compound Chinese medicine used for treating various cancers, such as lung cancer. However, the exact mechanism of its antilung cancer active ingredient remains unclear. This study aims to explore and validate the effective active ingredients and mechanism of action of BJOE in the treatment of lung cancer through network pharmacology, molecular docking technology, and cell experiments. The results showed that there were 13 active ingredients, 136 target genes, and 42 disease target-coexpressed genes in BJOE. The molecular docking results indicated that the main active components of the oil emulsion, YD1 (ß-sitosterol), YD2 (luteolin), and YD3 (bruceitol), could stably bind to TP53 and MAPK1. Furthermore, the commercially available ß-sitosterol luteolin was used as a representative compound to conduct cell experiments to verify its anticancer activity and mechanism. It was found that luteolin can inhibit the proliferation better than ß-sitosterol and the activity of lung cancer cells by regulating the expression of related proteins through the P53/MAPK1 signaling pathway. This study combines network pharmacology prediction with experiments to demonstrate the "multicomponent, multitarget, multipathway" approach of B. javanica oil emulsion in treating lung cancer.

Research progress on the regulation and mechanism of borneol on the blood-brain barrier in pathological states: a narrative review focused on ischemic stroke and cerebral glioma.

Background and Objective: The blood-brain barrier (BBB) serves as a dynamic, selective shield, safeguarding the central nervous system (CNS) by separating the brain from circulating blood, preserving its microenvironment, and ensuring stability. However, in the presence of brain pathology, drug delivery across the BBB and blood-tumor barrier (BTB) becomes challenging, hindering effective treatments. Borneol exhibits promise in bidirectionally modulating the BBB under pathological conditions, suggesting at potential clinical applications for related diseases. Our primary goal in this review is to investigate borneol's potential clinical utility in bidirectionally regulating the BBB under pathological conditions. Methods: The PubMed database, CNKI (China National Knowledge Infrastructure), Wanfang Data were searched to retrieve articles on animal experiments and cell-based research published from January 1, 2003, to May 1, 2023, using the following medical subject headings (MeSH) terms: borneol, blood-brain barrier, ischemic stroke, cerebral gliomas, anti-inflammatory. The search was limited to articles published in English and Chinese. In total, 86 articles were deemed eligible for inclusion in this study. Key Content and Findings: The breakdown of the BBB is a key pathological process in ischemic stroke and cerebral glioma. When used alone, the lipophilic properties of borneol can reduce the permeability of the BBB and restore its normal function, thereby repairing brain damage and protecting brain tissue. Its specific protective effects may be related to inflammatory regulation mechanisms. The anti-inflammatory and protective effects of borneol can be used to improve and treat lesions caused by ischemic stroke and cerebral glioma. Furthermore, when combined with other drugs, borneol can accelerate the opening of the BBB, improve permeability through physiological processes, and enhance drug penetration and distribution in the brain without causing pathological damage to the brain. Conclusions: This review summarizes the mechanisms by which borneol regulates the BBB and BTB in ischemic stroke and cerebral glioma, and discusses the potential clinical applications of borneol in the treatment of these diseases. It is believed that in the future, as research methods are refined, more effective and targeted therapies for cerebral glioma and ischemic stroke will be explored related to the protective mechanism of the BBB under pathological conditions with borneol alone or in combination with other drugs.

A Calibration-Free Hybrid BCI Speller System Based on High-Frequency SSVEP and sEMG.

Hybrid brain-computer interface (hBCI) systems that combine steady-state visual evoked potential (SSVEP) and surface electromyography (sEMG) signals have attracted attention of researchers due to the advantage of exhibiting significantly improved system performance. However, almost all existing studies adopt low-frequency SSVEP to build hBCI. It produces much more visual fatigue than high-frequency SSVEP. Therefore, the current study attempts to build a hBCI based on high-frequency SSVEP and sEMG. With these two signals, this study designed and realized a 32-target hBCI speller system. Thirty-two targets were separated from the middle into two groups. Each side contained 16 sets of targets with different high-frequency visual stimuli (i.e., 31-34.75 Hz with an interval of 0.25 Hz). sEMG was utilized to choose the group and SSVEP was adopted to identify intra-group targets. The filter bank canonical correlation analysis (FBCCA) and the root mean square value (RMS) methods were used to identify signals. Therefore, the proposed system allowed users to operate it without system calibration. A total of 12 healthy subjects participated in online experiment, with an average accuracy of 93.52 ± 1.66% and the average information transfer rate (ITR) reached 93.50 ± 3.10 bits/min. Furthermore, 12 participants perfectly completed the free-spelling tasks. These results of the experiments indicated feasibility and practicality of the proposed hybrid BCI speller system.

Vagus Nerve Stimulation Relives Irritable Bowel Syndrome and the Associated Depression via α7nAChR-mediated Anti-inflammatory Pathway.

OBJECTIVES: The present study is designed to investigate the role of vagus nerve in the treatments of irritable bowel syndrome (IBS) and the associated central nervous system disorders. METHODS: An IBS animal model was established by giving acetic acid and chronic-acute stress (AA-CAS) treatment in adult male Wistar rats. Subdiaphragmatic vagotomy (SDV) and vagus nerve stimulation (VNS) were performed to intervene the excitability of vagus nerve. Permeability of blood brain barrier (BBB) was measured and agonist and antagonist of α7 nicotinic acetylcholine receptor (α7nAChR) were used to explore the relevant mechanisms. RESULTS: AA-CAS treatment resulted in abnormal fecal output, increased visceral sensitivity, depressive-like behaviors, and overexpression of inflammatory mediators, all of which were reversed by VNS treatment. The effects of VNS could also be observed when α7nAChR agonist was applied. Whereas α7nAChR antagonist (methyllycaconitine, MLA) reversed VNS's effects. Interestingly, VNS also reduced the increased permeability of blood brain barrier (BBB) following AA-CAS treatment in IBS rats. SDV treatment only show temporary efficacy on AA-CAS-induced symptoms and had no effect on the permeability of BBB. CONCLUSION: The intestinal abnormalities and depressive symptoms in IBS rats can be improved by VNS treatment. This positive effect of VNS was achieved through α7nAChR-mediated inflammatory pathway and may also be associated with the decreased of BBB permeability.

Unveiling tumor immune evasion mechanisms: abnormal expression of transporters on immune cells in the tumor microenvironment.

The tumor microenvironment (TME) is a crucial driving factor for tumor progression and it can hinder the body's immune response by altering the metabolic activity of immune cells. Both tumor and immune cells maintain their proliferative characteristics and physiological functions through transporter-mediated regulation of nutrient acquisition and metabolite efflux. Transporters also play an important role in modulating immune responses in the TME. In this review, we outline the metabolic characteristics of the TME and systematically elaborate on the effects of abundant metabolites on immune cell function and transporter expression. We also discuss the mechanism of tumor immune escape due to transporter dysfunction. Finally, we introduce some transporter-targeted antitumor therapeutic strategies, with the aim of providing new insights into the development of antitumor drugs and rational drug usage for clinical cancer therapy.

Ecological risk assessment of aquatic organisms induced by heavy metals in the estuarine waters of the Pearl River.

With the rapid economic development of China's coastal areas and the growth of industry and population, the problem of heavy metal contamination in estuarine waters is increasing in sensitivity and seriousness. In order to accurately and quantitatively describe the current status of heavy metal contamination and identify sensitive aquatic organisms with high ecological risks, five heavy metals in eight estuaries of the Pearl River were monitored at monthly intervals from January to December in 2020, and the ecological risks of aquatic organisms induced by heavy metals were evaluated using Risk quotients (RQ) and species sensitivity distributions (SSD) methods. The results showed that the concentrations of As, Cu, Pb, Hg and Zn in estuaries of the Pearl River were (0.65-9.25) µg/L, (0.07-11.57) µg/L, (0.05-9.09) µg/L, (< 0.40) µg/L and (0.67-86.12) µg/L, respectively. With the exception of Hg in Jiaomen water, the other heavy metals in each sampling site met or exceed the water quality standard of Grade II. The aquatic ecological risks of As, Pb and Hg were generally low in the waters of the Pearl River estuary, but individual aquatic organisms are subject to elevated ecological risks due to Cu and Zn. The content of Zn has a lethal effect on the crustaceans Temora Stylifera, and the content of Cu has a serious impact on the mollusks Corbicula Fluminea and has a certain impact on the crustaceans Corophium sp. and the fish Sparus aurata. Heavy metal levels and joint ecological risks (msPAF) in the Humen, Jiaomen, Hongqimen, and Hengmen estuaries were slightly higher than in other estuaries, and the Yamen estuary had the lowest contration of heavy metals and ecological risk. Research findings can serve as a basis for formulating water quality standards for heavy metals and for protecting aquatic biodiversity in the Pearl River Estuary.

Global status of phenotypic pyrazinamide resistance in Mycobacterium tuberculosis clinical isolates: an updated systematic review and meta-analysis.

Pyrazinamide (PZA) is an essential first-line tuberculosis drug for its unique mechanism of action active against multidrug-resistant-TB (MDR-TB). Thus, the aim of updated meta-analysis was to estimate the PZA weighted pooled resistance (WPR) rate in M. tuberculosis isolates based on publication date and WHO regions. We systematically searched the related reports in PubMed, Scopus, and Embase (from January 2015 to July 2022). Statistical analyses were performed using STATA software. The 115 final reports in the analysis investigated phenotypic PZA resistance data. The WPR of PZA was 57% (95% CI 48-65%) in MDR-TB cases. According to the WHO regions, the higher WPRs of PZA were reported in the Western Pacific (32%; 95% CI 18-46%), South East Asian region (37%; 95% CI 31-43%), and the Eastern Mediterranean (78%; 95% CI 54-95%) among any-TB patients, high risk of MDR-TB patients, and MDR-TB patients, respectively. A negligible increase in the rate of PZA resistance were showed in MDR-TB cases (55% to 58%). The rate of PZA resistance has been rising in recent years among MDR-TB cases, underlines the essential for both standard and novel drug regimens development.

Construction of Metastasis-Specific Regulation Network in Ovarian Cancer Based on Prognostic Stemness-Related Signatures.

WE aimed to reveal the correlation between ovarian cancer (OV) metastasis and cancer stemness in OV. RNA-seq data and clinical information of 591 OV samples (551 without metastasis and 40 with metastasis) were obtained from TCGA. The edgeR method was used to determine differentially expressed genes (DEGs) and transcription factors (DETFs). Then, mRNA expression-based stemness index was calculated using one-class logistic regression (OCLR). Weighted gene co-expression network analysis (WGCNA) was used to define stemness-related genes (SRGs). Univariate and multivariate Cox proportional hazard regression were conducted to identify the prognostic SRGs (PSRGs). PSRGs, DETFs, and 50 hallmark pathways quantified by gene set variation analysis (GSVA) were integrated into Pearson co-expression analysis. Significant co-expression interactions were utilized to construct an OV metastasis-specific regulation network. Cell communication analysis was carried out based on single cell RNA sequencing data to explore the molecular regulation mechanism of OV. Eventually, assay for targeting accessible-chromatin with high throughout sequencing (ATAC), chromatin immunoprecipitation sequencing (ChIP-seq) validation, and multiple data sets were used to validate the expression levels and prognostic values of key stemness-related signatures. Moreover, connectivity map (CMap) was used to identify potential inhibitors of stemness-related signatures. Based on edgeR, WGCNA, and Cox proportional hazard regression, 22 PSRGs were defined to construct a prognostic prediction model for metastatic OV. In the metastasis-specific regulation network, key TF-PSRS interaction pair was NR4A1-EGR3 (correlation coefficient = 0.81, p < 0.05, positive), and key PSRG-hallmark pathway interaction pair was EGR3-TNFα signaling via NFκB (correlation coefficient = 0.44, p < 0.05, positive), which were validated in multi-omics databases. Thioridazine was postulated to be the most significant compound in treatment of OV metastasis. PSRGs played critical roles in OV metastasis. Specifically, EGR3 was the most significant PSRG, which was positively regulated by DETF NR4A1, inducing metastasis via TNFα signaling.

Metabolism and pharmacokinetic study of deuterated osimertinib.

Osimertinib is a highly selective third-generation irreversible inhibitor of epidermal growth factor receptor mutant, which can be utilized to treat non-small cell lung cancer. As the substrate of cytochrome P450 enzyme, it is mainly metabolized by the CYP3A enzyme in humans. Among the metabolites produced by osimertinib, AZ5104, and AZ7550, which are demethylated that is most vital. Nowadays, deuteration is a new design approach for several drugs. This popular strategy is deemed to improve the pharmacokinetic characteristics of the original drugs. Therefore, in this study the metabolism profiles of osimertinib and its deuterated compound (osimertinib-d3) in liver microsomes and human recombinant cytochrome P450 isoenzymes and the pharmacokinetics in rats and humans were compared. After deuteration, its kinetic isotope effect greatly inhibited the metabolic pathway that produces AZ5104. The plasma concentration of the key metabolite AZ5104 of osimertinib-d3 in rats and humans decreased significantly compared with that of the osimertinib. This phenomenon was consistent with the results of the metabolism studies in vitro. In addition, the in vivo results indicated that osimertinib-d3 had higher systemic exposure (AUC) and peak concentration (Cmax ) compared with the osimertinib in rats and human body.

Environmental, energy, and economic impact assessment of sludge management alternatives based on incineration.

In this study, different management strategies for sewage sludge disposal were evaluated associated with environmental, energy, and economic impact, using life cycle assessment (LCA), cumulative energy demand (CED) and life cycle costing (LCC) approaches. Four scenarios, including mono-incineration, co-incineration in municipal solid wastes (MSW) incineration plant, co-incineration in coal-fired power plant and co-incineration in cement kiln, were assessed. The environmental burdens generated from the sludge incineration contributed primarily to the global warming, followed by eutrophication, marine aquatic ecotoxicity, and human toxicity potential across the four scenarios. Furthermore, mono-incineration scenario appeared to be the most environmentally unfriendly, energy and economy intensive alternative, with the LCA, CED and LCC value of 5.41E-09, 1736 MJ and 1.84 million CNY, respectively. By contrast, co-incineration in cement kiln exhibited the lowest CED (368 MJ), LCC (0.59 million CNY), and environmental burdens (1.02E-09). In addition, the sensitivity analysis indicated that four scenarios were sensitive to the changes in the electricity efficiency and the moisture content contained in sewage sludge, suggesting that it was of great significance to enhance the efficiency of sludge dewatering and thermal drying The findings of this study can provide scientific reference for selecting the optimal strategies for the most environmentally and economically friendly sewage sludge management with optimum energy efficiency.

Highly efficient red-emitting carbon dots as a "turn-on" temperature probe in living cells.

Nanothermometers, which can precisely detect the intracellular temperature changes, have great potential to solve questions concerning the cellular processes. Thus, the temperature sensors that provide fluorescent "turn-on" signals in the biological transparency window are of highly desirable. To meet these criteria, this work reported a new "turn-on" carbon dot (CD)-based fluorescent nanothermometry device for sensing temperature in living cells. The CDs that emit bright red fluorescence (R-CDs; λmax = 610 nm in water) were synthesized with o-phenylenediamine as carbon precursor via a facile solvothermal method. The R-CDs in water were almost nonfluorescent at 15 °C. As the temperature increased, the fluorescence intensity of R-CDs exhibited a gradual increase and the final enhancement factor was greater than 21-fold. The fluorescence intensity exhibited a linear response to temperature and a high-sensitive variation of ≈13.3 % °C-1 was detected within a broad temperature range of 28-60 °C. Moreover, the R-CD thermal sensors also exhibited high storage stability, excellent response reversibility and superior photo- and thermo-stability. Due to its good biocompatibility and "intelligent" response to external temperature, the nanothermometer could be applied for sensing temperature changes in biological media.

Insights into CO2 adsorption on KOH-activated biochars derived from the mixed sewage sludge and pine sawdust.

The environment issues associated with global warming and climate change caused by continuous increase in greenhouse gas emissions have attracted worldwide concerns. As renewable resources with good adsorption property, biochar is an efficient and environmental friendly adsorbsent for CO2 capture. In this study, the CO2 adsorption behavior of biochars derived from feedstock mixtures of 70% pine sawdust and 30% sewage sludge by KOH modification was investigated. The textual properties and functional groups of the pristine biochars have been significantly enhanced after KOH activation. With highly developed microporosity, the specific surface area (SSA) of the KOH-modified biochars increased by 3.9-14.5 times. Furthermore, higher CO2 adsorption capacities of 136.7-182.0 mg/g were observed for the modified biochars, compared to pristine ones (35.5-42.9 mg/g). The development of micropores by KOH activation significantly increased the CO2 adsorption capacity. Meanwhile, the presence of hetero atoms (O and K) also positively influenced CO2 adsorption capacity of biochar. Noticeably, both physical and chemical adsorption played a crucial role in CO2 capture, which was verified by different characterization methods including high resolution scanning electron microscope, X-ray photoelectron spectroscopy and in situ diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy. The Findings of this study demonstrate the -significance of chemical sorption by identifying the transformation of CO2 by biochar composites and in situ characterization of weakly adsorbed and newly formed mineral species during the CO2 sorption process. Moreover, BC700K showed 97% recyclability during 10 consecutive adsorption-desorption cycles at 25 °C, 1 bar. The results obtained in the present study may inspire new research interest and provide a comprehensive insight into the research subject to biochars derived from feedstock mixtures for CO2 capture.

The role of periampullary diverticulum on the incidence of pancreaticobiliary diseases and the outcome of endoscopic retrograde cholangiopancreatography.

INTRODUCTION: Periampullary diverticulum (PAD), although commonly discovered in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP), remains controversial regarding its role in pancreaticobiliary diseases and the failure rate of cannulation. The aim of this study was to evaluate the association of PAD with pancreaticobiliary diseases and its impact on the outcome of ERCP. MATERIAL AND METHODS: A retrospective analysis was carried out on 1455 patients who underwent an ERCP. Patients were divided into a PAD group and a control group without PAD, and propensity score matching was performed to adjust for clinical differences. The comparison was focused on pancreaticobiliary diseases, technical success, and complications of ERCP. RESULTS: The occurrence of PAD is associated significantly with increasing age (p < 0.001). Incidences of acute pancreatitis (AP), suppurative cholangitis, and pancreatic head cancer were significantly higher in the PAD group (p < 0.05). After propensity score matching, the PAD group exhibited a higher rate of post-ERCP complications including haemorrhage, post-ERCP pancreatitis (PEP), and hyperamylasaemia (p < 0.05). However, the prevalence of perforation and the success rate of ERCP did not differ between groups (p > 0.05). CONCLUSIONS: Periampullary diverticulum develops with aging and seems to be associated with an increase in pancreaticobiliary diseases and post-ERCP complications except for perforation. Additionally, the presence of PAD does not affect the technical success of ERCP.

Magnetic properties of the surface sediments in the Yellow River Estuary and Laizhou Bay, Bohai Sea, China: Implications for monitoring heavy metals.

The Yellow River Estuary (YRE) and adjacent Laizhou Bay (LB) encounter eco-environmental risks caused by heavy metals (HMs) pollution. Here magnetic measurements were performed on 239 surface sediment samples from the YRE and LB to establish a rapid and effective method for detecting HMs. Magnetite, maghemite, and hematite coexist in the sediments. The distributions of magnetic minerals are dominated by sediment sources (Yellow River in northern and western LB, and rivers in southern and eastern coastal LB), and the anticlockwise water current. Compared to the background values, Cd content is enriched for all samples, while Co, Cr, Ni, Cu, Zn, and Pb contents are lower for most samples. The low pollution load indexes (PLI) of HMs (< 1-1.56) indicate the unpolluted to moderately polluted status, while the muddy area is the most polluted. The principal component analysis indicates that Co, Cr, Ni, Cu, and Zn are mainly from natural weathering substances, while Cd and Pb are anthropogenic. Contents of fine-grained sediments and magnetic particles are positively correlated to Co, Ni, Cu, Zn, and PLI. The high-risk Co, Ni, Cu, and Zn regions can be quickly delineated with the frequency-dependent susceptibility.

Diverse molecular compositions of dissolved organic matter derived from different composts using ESI FT-ICR MS.

Dissolved organic matter (DOM) derived from various composts can promote significant changes of soil properties. However, little is known about the DOM compositions and their similarities and differences at the molecular level. In this study, the molecular compositions of DOM derived from kitchen waste compost (KWC), green waste compost (GWC), manure waste compost (MWC), and sewage sludge compost (SSC) were characterized by electrospray ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS). The molecular formulas were classified into four subcategories: CHO, CHON, CHOS, and CHONS. The KWC, MWC, and SSC DOM represented the highest fraction (35.8%-47.4%) of CHON subcategory, while the GWC DOM represented the highest fraction (68.4%) of CHO subcategory. The GWC DOM was recognized as the nitrogen- and sulfur-deficient compounds that were less saturated, more aromatic, and more oxidized compared with other samples. Further analysis of the oxygen, nitrogen-containing (N-containing), and sulfur-containing (S-containing) functional groups in the four subcategories revealed higher organic molecular complexity. Comparison of the similarities and differences of the four samples revealed 22.8% ubiquitous formulas and 17.4%, 11.1%, 10.7%, and 6.3% unique formulas of GWC, KWC, SSC, and MWC DOM, respectively, suggesting a large proportion of ubiquitous DOM as well as unique, source-specific molecular signatures. The findings presented herein provide new insight into the molecular characterization of DOM derived from various composts and demonstrated the potential role of these different compounds for agricultural utilization.

Magnetic response of Arsenic pollution in a slag covered soil profile close to an abandoned tungsten mine, southern China.

Previous studies indicated serious soil arsenic (As) pollution of large spatial extent related to tungsten mining. We performed systematic analyses of magnetic parameters and As contents of a slag covered soil profile close to the abandoned tungsten mine in southern China, in order to discuss the feasibility of using sensitive, non-destructive, and cost-effective magnetic methods for monitoring the soil arsenic content in such arsenic pollution areas. The results indicate that arsenic sulfide entered from slags into the underlying soil and changed to iron arsenate and moveable arsenic ion. The arsenic ions were transported from the upper to the lower part of the soil profile, leading to more serious arsenic pollution at lower levels of the section. Pedogenesis and oxidation of the entered iron and arsenic sulfide resulted in coexistence of magnetite/maghemite and hematite, with different contributions at depths of 125-195 cm, 60-125 cm, and 0-60 cm. The arsenic content is significant positively correlated with the hematite concentration given by the magnetic parameter HIRM and negatively correlated with the S-300 ratio that measures the relative contributions of magnetite(+maghemite) and hematite. The S-300 ratio is effective for semi-quantification of soil arsenic content, and may be also used for soil arsenic pollution assessment and monitoring in similar settings of tungsten mining.

Potential effects of exploiting the Yunfu pyrite mine (southern China) on soil: evidence from analyzing trace elements in surface soil.

Trace element contamination caused by mining is a serious environmental problem. The potential effects of exploiting the Yunfu pyrite mine (southern China) on soil were investigated by determining trace elements in 56 surface soil samples from the vicinity of the Yunfu pyrite mine. The samples were acid dissolved and measured by an inductively coupled plasma mass spectrometry (ICP-MS). Principal component analysis and hierarchical cluster analysis were used to identify factors influencing the trace element contents and possible sources of the trace elements. The degree of trace element pollution was determined using the geological accumulation index Igeo. Monte Carlo simulations were used to assess the health risks posed. The results show that (1) six factors (parent material, mining activities, ore composition, rainfall, terrain, and other inputs) strongly affected the trace element contents of the soil samples. (2) There were three groups of trace elements, according to their possible sources. One group (Cs, Ga, Ge, Hf, Nb, Rb, Ta, Th, Ti, U, and Zr) mainly originated in parent rocks. Another group (Cr, Ni, Sr, and V) was mainly supplied by industrial plants and traffic emissions. The third group (Ba, Co, Cu, Mn, Pb, and Zn) was mainly supplied through pyrite ore exploitation processes. (3) Some samples were slightly to moderately polluted with Cs, Ga, Ge, Nb, Rb, Ta, and Ti. Most samples were moderately to highly polluted with Ba, Co, Cu, Mn, Pb, and Zn. (4) Trace elements in soil pose strong non-carcinogenic and carcinogenic health risks to people (particularly children) living near the Yunfu pyrite mine.

Fucoxanthin prevents lipopolysaccharide-induced depressive-like behavior in mice via AMPK- NF-κB pathway.

Fucoxanthin (FX), a natural carotenoid abundant in edible brown seaweeds, has been shown the great anti-oxidant, anti-inflammatory and anti-diabetic effects in vivo and in vitro. The present study was designed to investigate the effects of FX on lipopolysaccharide (LPS)-induced behavioral defects in mice. In depressive behavior tests, the increased immobility time of forced swimming test and tail suspension test by LPS treatment in mice, which were significantly reversed by FX treatment (200 mg/kg, i.g.). In anxiety behavior tests, LPS injection was neither influence the anxiety-related parameters in marble burying test nor that in elevated plus maze test. Interestingly, anxiolytic effects were observed in single FX treated control and LPS-induced mice groups. FX treatment also reversed LPS-induced body weight loss and food intake decreases. Biochemical analysis indicated that FX inhibited LPS-induced overexpression of pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α), as well as iNOS and COX-2 in the hippocampus, frontal cortex and hypothalamus, via the modulation of AMPK-NF-κB signaling pathway.

Biochemical and hemostatic mechanism of a novel thrombin-like enzyme.

Thrombin-like enzyme (TLE) plays a significant role in vessel injury hemostasis. A novel snake venom TLE (Agacutin) was purified from Agkistrodon Acutus snake venom. Structural analysis indicated that Agacutin is a heterodimer that has a MW of 29,402 Da, a pI value of 5.39, and optimum activity at 35 degrees C and pH 7.5. The N-terminal 15 amino acid sequences of Agacutin are DSSGWSSYEGHEYYV (small subunit) and DCSSGWSSYEEHQYY (large subunit). In vitro studies indicated that the coagulation activity of Agacutin was activated by Ca(+2) or inhibited by phenylmethanesulfonyl fluoride, but not influenced by heparin or hirudin. The arginine esterase activity and fibrinogen hydrolysis result showed that Agacutin only cleaves alpha-subunit and releases fibrinopeptide A. In vivo studies indicated that Agacutin iv (0.01-0.05 U/kg) shortened 30.2-49% of the rabbit blood clotting time, or ip (0.5-2.0 U/kg) shortened 29.7-73.1% of the mouse tail bleeding time. Agacutin does not influence APTT, platelet or euglobulin clotting time, and activate Factor II or XIII. It converts fibrinogen into the soluble fibrin that accelerates hemostasis at wound.