Pparα activation stimulates autophagic flux through lipid catabolism-independent route.

Autophagy is a cellular process that involves the fusion of autophagosomes and lysosomes to degrade damaged proteins or organelles. Triglycerides are hydrolyzed by autophagy, releasing fatty acids for energy through mitochondrial fatty acid oxidation (FAO). Inhibited mitochondrial FAO induces autophagy, establishing a crosstalk between lipid catabolism and autophagy. Peroxisome proliferator-activated receptor α (PPARα), a transcription factor, stimulates lipid catabolism genes, including fatty acid transport and mitochondrial FAO, while also inducing autophagy through transcriptional regulation of transcription factor EB (TFEB). Therefore, the study explores whether PPARα regulates autophagy through TFEB transcriptional control or mitochondrial FAO. In aquaculture, addressing liver lipid accumulation in fish is crucial. Investigating the link between lipid catabolism and autophagy is significant for devising lipid-lowering strategies and maintaining fish health. The present study investigated the impact of dietary fenofibrate and L-carnitine on autophagy by activating Pparα and enhancing FAO in Nile tilapia (Oreochromis niloticus), respectively. The dietary fenofibrate and L-carnitine reduced liver lipid content and enhanced ATP production, particularly fenofibrate. FAO enhancement by L-carnitine showed no changes in autophagic protein levels and autophagic flux. Moreover, fenofibrate-activated Pparα promoted the expression and nuclear translocation of Tfeb, upregulating autophagic initiation and lysosomal biogenesis genes. Pparα activation exhibited an increasing trend of LC3II protein at the basal autophagy and cumulative p62 protein trends after autophagy inhibition in zebrafish liver cells. These data show that Pparα activation-induced autophagic flux should be independent of lipid catabolism.

Prognostic Prediction Value and Biological Functions of Non-Apoptotic Regulated Cell Death Genes in Lung Adenocarcinoma.

Objective To explore the potential biological functions and prognostic prediction values of non-apoptotic regulated cell death genes (NARCDs) in lung adenocarcinoma.Methods Transcriptome data of lung adenocarcinoma were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. We identified differentially expressed NARCDs between lung adenocarcinoma tissues and normal tissues with R software. NARCDs signature was constructed with univariate Cox regression analysis and the least absolute shrinkage and selection operator Cox regression. The prognostic predictive capacity of NARCDs signature was assessed by Kaplan-Meier survival curve, receiver operating characteristic curve, and univariate and multivariate Cox regression analyses. Functional enrichment of NARCDs signature was analyzed with gene set variation analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. In addition, differences in tumor mutational burden, tumor microenvironment, tumor immune dysfunction and exclusion score, and chemotherapeutic drug sensitivity were analyzed between the high and low NARCDs score groups. Finally, a protein-protein interaction network of NARCDs and immune-related genes was constructed by STRING and Cytoscape software. Results We identified 34 differentially expressed NARCDs associated with the prognosis, of which 16 genes (ATIC, AURKA, CA9, ITGB4, DDIT4, CDK5R1, CAV1, RRM2, GAPDH, SRXN1, NLRC4, GLS2, ADRB2, CX3CL1, GDF15, and ADRA1A) were selected to construct a NARCDs signature. NARCDs signature was identified as an independent prognostic factor (P < 0.001). Functional analysis showed that there were significant differences in mismatch repair, p53 signaling pathway, and cell cycle between the high NARCDs score group and low NARCDs score group (all P < 0.05). The NARCDs low score group had lower tumor mutational burden, higher immune score, higher tumor immune dysfunction and exclusion score, and lower drug sensitivity (all P < 0.05). In addition, the 10 hub genes (CXCL5, TLR4, JUN, IL6, CCL2, CXCL2, ILA, IFNG, IL33, and GAPDH) in protein-protein interaction network of NARCDs and immune-related genes were all immune-related genes. Conclusion The NARCDs prognostic signature based on the above 16 genes is an independent prognostic factor, which can effectively predict the clinical prognosis of patients of lung adenocarcinoma and provide help for clinical treatment.

The Adaptive Characteristics of Cholesterol and Bile Acid Metabolism in Nile Tilapia Fed a High-Fat Diet.

Since high-fat diet (HFD) intake elevates liver cholesterol and enhanced cholesterol-bile acid flux alleviates its lipid deposition, we assumed that the promoted cholesterol-bile acid flux is an adaptive metabolism in fish when fed an HFD. The present study investigated the characteristic of cholesterol and fatty acid metabolism in Nile tilapia (Oreochromis niloticus) after feeding an HFD (13% lipid level) for four and eight weeks. Visually healthy Nile tilapia fingerlings (average weight 3.50 ± 0.05 g) were randomly distributed into four treatments (4-week control diet or HFD and 8-week control diet or HFD). The liver lipid deposition and health statue, cholesterol/bile acid, and fatty acid metabolism were analyzed in fish after short-term and long-term HFD intake. The results showed that 4-week HFD feeding did not change serum alanine transaminase (ALT) and aspartate transferase (AST) enzyme activities, along with comparable liver malondialdehyde (MDA) content. But higher serum ALT and AST enzyme activities and liver MDA content were observed in fish fed 8-week HFD. Intriguingly, remarkably accumulated total cholesterol (mainly cholesterol ester, CE) was observed in the liver of fish fed 4-week HFD, along with slightly elevated free fatty acids (FFAs) and comparable TG contents. Further molecular analysis in the liver showed that obvious accumulation of CE and total bile acids (TBAs) in fish fed 4-week HFD was mainly attributed to the enhancement of cholesterol synthesis, esterification, and bile acid synthesis. Furthermore, the increased protein expressions of acyl-CoA oxidase 1/2 (Acox1 and Acox2), which serve as peroxisomal fatty acid ß-oxidation (FAO) rate-limiting enzymes and play key roles in the transformation of cholesterol into bile acids, were found in fish after 4-week HFD intake. Notably, 8-week HFD intake remarkably elevated FFA content (about 1.7-fold increase), and unaltered TBAs were found in fish liver, accompanied by suppressed Acox2 protein level and cholesterol/bile acid synthesis. Therefore, the robust cholesterol-bile acid flux serves as an adaptive metabolism in Nile tilapia when fed a short-term HFD and is possibly via stimulating peroxisomal FAO. This finding enlightens our understanding on the adaptive characteristics of cholesterol metabolism in fish fed an HFD and provides a new possible treatment strategy against metabolic disease induced by HFD in aquatic animals.

Mildronate triggers growth suppression and lipid accumulation in largemouth bass (Micropterus salmoides) through disturbing lipid metabolism.

Many metabolic diseases in fish are often associated with lowered mitochondrial fatty acid ß-oxidation (FAO). However, the physiological role of mitochondrial FAO in lipid metabolism has not been verified in many carnivorous fish species, for example in largemouth bass (Micropterus salmonids). In the present study, a specific mitochondrial FAO inhibitor, mildronate (MD), was used to investigate the effects of impaired mitochondrial FAO on growth performance, health status, and lipid metabolism of largemouth bass. The results showed that the dietary MD treatment significantly suppressed growth performance and caused heavy lipid accumulation, especially neutral lipid, in the liver. The MD-treated fish exhibited lower monounsaturated fatty acid and higher long-chain polyunsaturated fatty acids in the muscle. The MD treatment downregulated the gene expressions in lipolysis and lipogenesis, as well as the expressions of the genes and some key proteins in FAO without enhancing peroxisomal FAO. Additionally, the MD-treated fish had lower serum aspartate aminotransferase activity and lower pro-inflammation- and apoptosis-related genes in the liver. Taken together, MD treatment markedly induced lipid accumulation via depressing lipid catabolism. Our findings reveal the pivotal roles of mitochondrial FAO in maintaining health and lipid homeostasis in largemouth bass and could be hopeful in understanding metabolic diseases in farmed carnivorous fish.

Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation.

The farnesoid X receptor (FXR) is a ligand-activated transcription factor that plays important roles in regulating bile acid homeostasis. The aim of the present study was to investigate the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, carbon tetrachloride (CCl4)-induced acute liver injury. Mice were intraperitoneally injected with CCl4 (0.15ml/kg). In CCl4+OCA group, mice were orally with OCA (5mg/kg) 48, 24 and 1h before CCl4. As expected, hepatic FXR was activated by OCA. Interestingly, OCA pretreatment alleviated CCl4-induced elevation of serum ALT and hepatic necrosis. Moreover, OCA pretreatment inhibited CCl4-induced hepatocyte apoptosis. Additional experiment showed that OCA inhibits CCl4-induced hepatic chemokine gene Mcp-1, Mip-2 and Kc. Moreover, OCA inhibits CCl4-induced hepatic pro-inflammatory gene Tnf-α and Il-1ß. By contrast, OCA pretreatment elevated hepatic anti-inflammatory gene Il-4. Further analysis showed that OCA pretreatment inhibited hepatic IκB phosphorylation and blocked nuclear translocation of NF-κB p65 and p50 subunits during CCl4-induced acute liver injury. In addition, OCA pretreatment inhibited hepatic Akt, ERK and p38 phosphorylation in CCl4-induced acute liver injury. These results suggest that OCA protects against CCl4-induced acute liver injury and inflammation. Synthetic FXR agonists may be effective antidotes for hepatic inflammation during acute liver injury.

[Chemical Constituents from Infructescence of Platycarya strobilacea].

Objective: To study the chemical constituents of the chloroform and acetic ether fractions from infructescence of Platycarya strobilacea. Methods: The compounds were isolated and purified by various chromatographic methods. Spectral analysis were taken to identify the structures. Results: Eleven compounds were isolated and identified as dotriacontane( 1), ursolic acid( 2),hexacosene( 3),ß-sitosterol( 4),daucosterol( 5),2,5,8-trihydroxy-3-methoxy-1,4-naphthalenedione( 6),3,3'-dimethoxyellagic acid( 7),ellagic acid( 8),4'-hydroxyisoflavone-7-O-ß-D-galactoside( 9),3,3'-dimethoxyellagic acid-4'-O-ß-D-xylopyroside( 10), gallic acid( 11). Conclusion: Compounds 1,3 ~ 6,9,10 are isolated from this genus for the first time, compounds 1 ~ 6,9,10 are isolated from this plant for the first time.

MicroRNA-30b functions as a tumour suppressor in human colorectal cancer by targeting KRAS, PIK3CD and BCL2.

Colorectal cancer (CRC) is the third most common cancer in the USA. MicroRNAs play important roles in the pathogenesis of CRC. In this study, we investigated the role of miR-30b in CRC and found that its expression was significantly lower in CRC tissues than that in normal tissues. We showed that a low expression level of miR-30b was closely related to poor differentiation, advanced TNM stage and poor prognosis of CRC. Further experiments showed that over-expression of miR-30b suppressed CRC cell proliferation in vitro and tumour growth in vivo. Specifically, miR-30b promoted G1 arrest and induced apoptosis. Moreover, KRAS, PIK3CD and BCL2 were identified as direct and functional targets of miR-30b. MiR-30b directly targeted the 3'-untranslated regions of their mRNAs and repressed their expression. This study revealed functional and mechanistic links between miRNA-30b and oncogene KRAS, PIK3CD and BCL2 in the pathogenesis of CRC. MiR-30b not only plays important roles in the regulation of cell proliferation and tumour growth in CRC, but is also a potential prognostic marker or therapeutic target for CRC. Restoration of miR-30b expression may represent a promising therapeutic approach for targeting malignant CRC.

Metastasis-Associated in Colon Cancer-1 Associates With Poor Prognosis and Promotes Cell Invasion and Angiogenesis in Human Cervical Cancer.

OBJECTIVE: The aim of this study is to investigate the clinicopathologic significance and potential role of metastasis-associated in colon cancer-1 (MACC1) in the progression of cervical cancer. METHODS: MACC1 expression was examined in cervical cancer cell lines, 6 matched cervical cancer tissues, and adjacent noncancerous tissues using Western blotting and real-time reverse transcriptase polymerase chain reaction. MACC1 protein expression and localization were determined in 181 paraffin-embedded archived cervical cancer samples using immunohistochemistry. Statistical analyses were applied to evaluate the clinicopathologic significance. The effects of MACC1 on cell migration, invasion, and angiogenesis were examined using migration assay, wound healing assay, 3-dimensional morphogenesis assay, and chicken chorioallantoic membrane assay. Western blotting was performed to examine the impact of MACC1 on the Akt and nuclear factor κB signaling pathways. RESULTS: Both protein and messenger RNA levels of MACC1 was up-regulated in cervical cancer cell lines and cervical cancer tissues, as compared with normal tissues. High MACC1 expression was detected in 96 (53%) of 181 of the cervical cancer tissues. In addition, high MACC1 expression correlated significantly with aggressiveness of cervical cancer, including International Federation of Gynecology and Obstetric stage (P = 0.001), pelvic lymph node metastasis (P = 0.004), recurrence (P = 0.037), and poor survival (P = 0.001). Moreover, enforced expression of MACC1 in cervical cancer cell lines significantly enhanced cell migration, invasion, and angiogenesis. Conversely, knockdown of MACC1 caused an inhibition of cell migration, invasion, and angiogenesis. Up-regulation of MACC1 increased, but knockdown of MACC1 decreased the expression of matrix metalloproteinase-2 and matrix metalloproteinase-9. Furthermore, enforced expression of MACC1 could enhance, but knockdown of MACC1 could reduce AKT and nuclear factor κB pathway activity. CONCLUSIONS: Our findings suggest that MACC1 protein, as a valuable marker of cervical cancer prognosis, plays an important role in the progression of human cervical cancer cells.

Association between blood arsenic concentration and dyslipidemia: Mediating effect of lipid peroxidation in the elderly.

BACKGROUND: The earlier investigations have revealed heavy metals exposure is implicated in the pathogenesis of dyslipidemia. The goal was to evaluated the relationship of blood arsenic (As) concentration with dyslipidemia in the elderly through a cross-sectional study. METHODS: The entire 360 elderly population were selected. Fasting blood specimens, demographic information, and clinical characteristics were obtained. The concentration of blood As was detected using ICP-MS. Serum 8-iso-PGF2α, a biomarker of lipid peroxidation, was measured by ELISA. RESULTS: Pearson correlative analysis hinted there were strong relationships of blood As with liver function indices in the elderly. Besides, blood As was positively associated with total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), and apolipoprotein A-I (ApoA I). Further multivariate linear and logistic regression suggested that the incidences of TC and LDL-C elevation were upregulated with the rising tertiles of blood As. Blood As was positively related with the prevalence of dyslipidemia (OR=3.609; 95%CI: 1.353, 6.961). Additionally, serum 8-iso-PGF2α was dramatically and positively linked to the levels of blood As and lipid profiles. Mediation analyses verified that 8-iso-PGF2α partially mediated the correlations between blood As with TC (36.63%) and LDL-C (34.03%). CONCLUSION: Blood As concentration is positively related to lipid profiles in the elderly. Higher blood As concentration elevates the prevalence of dyslipidemia. Lipid peroxidation partially mediates the correlation of As exposure with dyslipidemia.

Inhibiting mitochondrial citrate shuttling induces hepatic triglyceride deposition in Nile tilapia (Oreochromis niloticus) through lipid anabolic remodeling.

The solute carrier family 25 member 1 (Slc25a1)-dependent mitochondrial citrate shuttle is responsible for exporting citrate from the mitochondria to the cytoplasm for supporting lipid biosynthesis and protein acetylation. Previous studies on Slc25a1 concentrated on pathological models. However, the importance of Slc25a1 in maintaining metabolic homeostasis under normal nutritional conditions remains poorly understood. Here, we investigated the mechanism of mitochondrial citrate shuttle in maintaining lipid metabolism homeostasis in male Nile tilapia (Oreochromis niloticus). To achieve the objective, we blocked the mitochondrial citrate shuttle by inhibiting Slc25a1 under normal nutritional conditions. Slc25a1 inhibition was established by feeding Nile tilapia with 250 mg/kg 1,2,3-benzenetricarboxylic acid hydrate for 6 weeks or intraperitoneal injecting them with dsRNA to knockdown slc25a1b for 7 days. The Nile tilapia with Slc25a1 inhibition exhibited an obesity-like phenotype accompanied by fat deposition, liver damage and hyperglycemia. Moreover, Slc25a1 inhibition decreased hepatic citrate-derived acetyl-CoA, but increased hepatic triglyceride levels. Furthermore, Slc25a1 inhibition replenished cytoplasmic acetyl-CoA through enhanced acetate pathway, which led to hepatic triglycerides accumulation. However, acetate-derived acetyl-CoA caused by hepatic Slc25a1 inhibition did not activate de novo lipogenesis, but rather modified protein acetylation. In addition, hepatic Slc25a1 inhibition enhanced fatty acids esterification through acetate-derived acetyl-CoA, which increased Lipin1 acetylation and its protein stability. Collectively, our results illustrate that inhibiting mitochondrial citrate shuttle triggers lipid anabolic remodeling and results in lipid accumulation, indicating the importance of mitochondrial citrate shuttle in maintaining lipid metabolism homeostasis.

Cobalt exposure and dyslipidemia in elderly population: the mediating role of systemic inflammation and lipid peroxidation.

Heavy metal exposure has been reported to be correlated with lipid profile alteration and dyslipidemia. While the associations between serum cobalt (Co) with lipid profile levels and risk of dyslipidemia have not been explored in elderly population, and the underlying mechanisms remain unclear. All eligible 420 elderly people were recruited in three communities of Hefei City in this cross-sectional study. Peripheral blood samples and clinical information were collected. The level of serum Co was detected through ICP-MS. The biomarkers for systemic inflammation (TNF-α) and lipid peroxidation (8-iso-PGF2α) were measured with ELISA. Each 1-unit increase of serum Co was related with 0.513 mmol/L, 0.196 mmol/L, 0.571 mmol/L, and 0.303 g/L in TC, TG, LDL-C, and ApoB, respectively. Multivariate linear and logistic regression analyses indicated that the prevalence of elevated TC, elevated LDL-C, and elevated ApoB were gradually increased according to tertiles of serum Co concentration (all P trend < 0.001). The risk of dyslipidemia was positively correlated with serum Co (OR = 3.500; 95% CI 1.630 ~ 7.517). Moreover, the levels of TNF-α and 8-iso-PGF2α were gradually risen in parallel with elevating serum Co. The elevation of TNF-α and 8-iso-PGF2α partially mediated Co-caused elevation of TC and LDL-C. Environmental Co exposure is associated with elevated lipid profile levels and dyslipidemia risk among elderly population. Systemic inflammation and lipid peroxidation partially mediate the associations of serum Co with dyslipidemia.

Double-edged effect of sodium citrate in Nile tilapia (Oreochromis niloticus): Promoting lipid and protein deposition vs. causing hyperglycemia and insulin resistance.

Citrate is an essential substrate for energy metabolism that plays critical roles in regulating glucose and lipid metabolic homeostasis. However, the action of citrate in regulating nutrient metabolism in fish remains poorly understood. Here, we investigated the effects of dietary sodium citrate on growth performance and systematic energy metabolism in juvenile Nile tilapia (Oreochromis niloticus). A total of 270 Nile tilapia (2.81 ± 0.01 g) were randomly divided into three groups (3 replicates per group, 30 fish per replicate) and fed with control diet (35% protein and 6% lipid), 2% and 4% sodium citrate diets, respectively, for 8 weeks. The results showed that sodium citrate exhibited no effect on growth performance (P > 0.05). The whole-body crude protein, serum triglyceride and hepatic glycogen contents were significantly increased in the 4% sodium citrate group (P < 0.05), but not in the 2% sodium citrate group (P > 0.05). The 4% sodium citrate treatment significantly increased the serum glucose and insulin levels at the end of feeding trial and also in the glucose tolerance test (P < 0.05). The 4% sodium citrate significantly enhanced the hepatic phosphofructokinase activity and inhibited the expression of pyruvate dehydrogenase kinase isozyme 2 and phosphor-pyruvate dehydrogenase E1 component subunit alpha proteins (P < 0.05). Additionally, the 4% sodium citrate significantly increased hepatic triglyceride and acetyl-CoA levels, while the expressions of carnitine palmitoyl transferase 1a protein were significantly down-regulated by the 4% sodium citrate (P < 0.05). Besides, the 4% sodium citrate induced crude protein deposition in muscle by activating mTOR signaling and inhibiting AMPK signaling (P < 0.05). Furthermore, the 4% sodium citrate significantly suppressed serum aspartate aminotransferase and alanine aminotransferase activities, along with the lowered expression of pro-inflammatory genes, such as nfκb, tnfα and il8 (P < 0.05). Although the 4% sodium citrate significantly increased phosphor-nuclear factor-kB p65 protein expression (P < 0.05), no significant tissue damage or inflammation occurred. Taken together, dietary supplementation of sodium citrate could exhibit a double-edged effect in Nile tilapia, with the positive aspect in promoting nutrient deposition and the negative aspect in causing hyperglycemia and insulin resistance.

The occurrence of "yellowing" phenomenon and its main driving factors after the remediation of chromium (Cr)-contaminated soils: A literature review.

Chromium (Cr) is a highly toxic element, which is widely present in environment due to industrial activities. One of most applicable technique to clean up Cr pollution is chemical reduction. However, the Cr(VI) concentration in soil increases again after remediation, and meanwhile the yellow soil would appear, which is commonly called as "yellowing" phenomenon. To date, the reason behind the phenomenon has been disputed for decades. This study aimed to introduce the possible "yellowing" mechanism and the influencing factors based on the extensive literature review. In this work, the concept of "yellowing" phenomenon was explained, and the most potential reasons include the reoxidation of manganese (Mn) oxides and mass transfer were summarized. Based on the reported finding and results, the large area of "yellowing" is likely to be caused by the re-migration of Cr(VI), since it could not sufficiently contact with the reductant under the effects of the mass transfer. In addition, other driving factors also control the occurrence of "yellowing" phenomenon. This review provides valuable reference for the academic peers participating in the Cr-contaminated sites remediation.

Dragon's Blood Inhibits Chronic Inflammatory and Neuropathic Pain Responses by Blocking the Synthesis and Release of Substance P in Rats.

As a traditional Chinese medicine, dragon's blood (DB) is widely used in treating various pains for thousands of years due to its potent anti-inflammatory and analgesic effects. In the present study, we observed that intragastric administration of DB at dosages of 0.14, 0.56, and 1.12 g/kg potently inhibited paw edema, hyperalgesia, cyclooxygenase-2 (COX-2) protein expression, or preprotachykinin-A mRNA expression in carrageenan-inflamed or sciatic nerve-injured (chronic constriction injury) rats, respectively. A short-term (15 s or 10 min) pre-exposure of cultured rat dorsal root ganglion (DRG) neurons to DB (0.3, 3, and 30 µg/ml) or its component cochinchinenin B (CB; 0.1, 1, and 10 µM) blocked capsaicin-evoked increases in both the intracellular calcium ion concentration and the substance P release. Moreover, a long-term (180 min) exposure of cultured rat DRG neurons to DB or CB significantly attenuated bradykinin-induced substance P release. These findings indicate that DB exerts anti-inflammatory and analgesic effects by blocking the synthesis and release of substance P through inhibition of COX-2 protein induction and intracellular calcium ion concentration. Therefore, DB may serve as a promising potent therapeutic agent for treatment of chronic pain, and its effective component CB might partly contribute to anti-inflammatory and analgesic effects.

Dragon's blood inhibits chronic inflammatory and neuropathic pain responses by blocking the synthesis and release of substance P in rats.

As a traditional Chinese medicine, dragon's blood (DB) is widely used in treating various pains for thousands of years due to its potent anti-inflammatory and analgesic effects. In the present study, we observed that intragastric administration of DB at dosages of 0.14, 0.56, and 1.12 g/kg potently inhibited paw edema, hyperalgesia, cyclooxygenase-2 (COX-2) protein expression, or preprotachykinin-A mRNA expression in carrageenan-inflamed or sciatic nerve-injured (chronic constriction injury) rats, respectively. A short-term (15 s or 10 min) pre-exposure of cultured rat dorsal root ganglion (DRG) neurons to DB (0.3, 3, and 30 µg/ml) or its component cochinchinenin B (CB; 0.1, 1, and 10 µM) blocked capsaicin-evoked increases in both the intracellular calcium ion concentration and the substance P release. Moreover, a long-term (180 min) exposure of cultured rat DRG neurons to DB or CB significantly attenuated bradykinin-induced substance P release. These findings indicate that DB exerts anti-inflammatory and analgesic effects by blocking the synthesis and release of substance P through inhibition of COX-2 protein induction and intracellular calcium ion concentration. Therefore, DB may serve as a promising potent therapeutic agent for treatment of chronic pain, and its effective component CB might partly contribute to anti-inflammatory and analgesic effects.

The effect of TRAIL on the expression of multidrug resistant genes MDR1, LRP and GST-π in drug-resistant gastric cancer cell SGC7901/VCR.

BACKGROUND/AIMS: To investigate the effect of tumor necrosis factor related apoptosis inducing ligand(TRAIL) on the expression of multidrug resistant genes MDR1, LRP and GST-n in drug-resistant gastric cancer cell strain SGC7901/VCR, and discuss a potential mechanism that reverses the multidrug resistance of gastric cancer with TRAIL as the target point. METHODOLOGY: SGC7901/VCR cell strain was treated over 48 h with TRAIL (50, 100, 200 and 400ig/L, respectively). The expression ofMDR1, LRP, GST-r mRNA in different groups of gastric cell strains was tested by RT-PCR and the expression of P-gp, LRP and GST-n by ELISA. RESULTS: Under the action of TRAIL of different concentrations, different degrees of inhibition were observed in the expression of the mRNA and protein, and the difference from the reference group was statistically significant(p<0.01). Except for the insignificant inhibition degree of mRNA and protein in MDR1, LRP and GST-nr as compared between the 400lg/L and the 2001ig/L group(p>0.05), the differences between other groups were all statistically significant (p<0.05). CONCLUSIONS: As preliminarily estimated from the results of the study, TRAILis negatively correlated with drug-resistant genes. It is possible that TRAIL increases the apoptosis and growth inhibition of chemotherapy drug tumor cells by reducing the expression of drug-resistant genes MDR1, LRP and GST-Tt, thereby participating in the reversion of the multidrug resistance of gastric cancer

[Study on chemical constituents of root bark of Discocleidion rufescens].

OBJECTIVE: To study the chemical constituents from root bark of Discocleidion rufescens. METHODS: Column chromatography and spectral analysis were used to isolate and identify the constituents. RESULTS: Ten compounds were obtained and identified from root bark of Discocleidion rufescens including beta-sitosterol (I), scopoletin (II), daucosterol (III), ricinine (IV), chrysophanol (V), aphyscion (VI), taraxerol (VII), pigenin (VIII), luteolin (IX), gallic acid (X). CONCLUSION: Ten compounds are isolated for the first time from root bark of Discocleidion rufescens. The monomer of Compounds II is isolated from this genus for the first time.

The geochemical behaviors of potentially toxic elements in a typical lead/zinc (Pb/Zn) smelter contaminated soil with quantitative mineralogical assessments.

This study comprehensively investigated the potential roles of soil mineralogy identified by the automated mineral liberation analysers (MLA) in the prediction of geochemical behavior of toxic metals in the smelter polluted soils. The results from modal mineralogy revealed that the non-reactive silicate phases such as quartz (42.05%) and biotite (40.43%) were the major mineralogical phases. The element deportment showed that fayalite, lead oxide, apatite, galena and wollastonite were identified as the dominant As, Cd, Pb and Zn bearing minerals. Furthermore, MLA analysis also confirmed that Pb was most concentrated in the smaller particles of lead oxide, which significantly enhanced Pb release in reaction with the chemical extractant during chemical kinetic tests. The results from pH-dependent leaching tests indicated that the leaching concentrations of As, Pb and Zn increased at low and high pH values, but were lowest at the neutral pH range. In addition, the results from the kinetic study demonstrated that the second order model provided the best description for the release patterns of the main metal contaminants in the bioavailability and bioaccessibility tests. The integrated geochemical analysis demonstrated that among these studied elements, As showed a typical geochemical pattern, which was predominantly controlled by 90.09% of fayalite. The above study results would have significant implications for soil remediation and risk management of smelter contaminated sites.

[Studies on the chemical constituents from the flowers of Ophiopogon japonicus].

OBJECTIVE: To study the chemical constituents from the flowers of Ophiopogon japonicus. METHODS: Column chromatography and spectral analysis were used to isolate and identify the constituents. RESULTS: Eleven compounds were obtained and identified as beta-sitosterol (I), diosgenin (II), daucosterol (III), ophiopogonin C' (IV), dioscin (V), 7-dihy-droxy-6-methyl-3-(4'-hydroxybenzyl) chroman-4-one(VI), luteolin (VII), kaempferol-3-O-beta-D-glucopyranosides (VIII), kaempferol-3-O-(6"-tigloyl) -beta-D-glucopyranosides (IX), kaempferol-3-O-(6"-acetyl) -beta-D-glucopyranosides (X), glucose (XI). CONCLUSION: Eleven compounds are obtained from the flowers of O. japonicus for the first time. Compond VI is isolated as a simple substance compound of O. japonicus for the first time. Componds VII, VIII, IX and X are isolated from this genus for the first time.

[Chemical constituents of flavonoids from flowers of Koelreuteria paniculata].

OBJECTIVE: To study the chemical constituents from flowers of Koelreuteria paniculata. METHODS: Column chromatography and spectral analysis were used to isolate and identify the constituents. RESULTS: The EtOAc fraction from flowers of Koelreuteria paniculata was separated and purified. Nine compounds were obtained and identified as:sitosterol glucoside (I), gallic acid (II), kaempferol (III), luteolin (IV), kaempferol-3-O-(6"-acetyl)-beta-D-glucopyranoside (V), hyperoside-2"-O-acetyl (VI), hyperoside-2"-O-galloyl (VII), hyperoside (VIII), kaempferol-3-O-D-glucopyranoside (IX). CONCLUSION: Nine compounds are isolated for the first time from flowers of Koelreuteria paniculata. Compounds IV, V, VI and IX are isolated from this genus for the first time.