Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer and a significant cause of cancer-related mortality globally. Resistance to chemotherapy, especially during CRC treatment, leads to reduced effectiveness of drugs and poor patient outcomes. Long noncoding RNAs (lncRNAs) have been implicated in various pathophysiological processes of tumor cells, including chemotherapy resistance, yet the roles of many lncRNAs in CRC remain unclear. AIM: To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance. METHODS: Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance. Various bioinformatics tools were employed to elucidate molecular mechanisms. The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction. Functional assays, including MTT, wound healing, and Transwell, were conducted to investigate the functional implications of lncRNA alterations. Interactions between lncRNAs and transcription factors were examined using RIP and luciferase reporter assays, while Western blotting was used to confirm downstream pathways. Additionally, a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance. RESULTS: LncRNA prion protein testis specific (PRNT) was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2 (HIPK2) expression. PRNT was demonstrated to sponge transcription factor zinc finger protein 184 (ZNF184), which in turn could regulate HIPK2 expression. Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin, with overexpression leading to decreased sensitivity and decreased expression reducing resistance. Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT. The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo. CONCLUSION: The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184. This regulatory mechanism enhances CRC progression and resistance to oxaliplatin, positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.

Three new species of Cortinarius section Delibuti (Cortinariaceae, Agaricales) from China.

Three new species of CortinariussectionDelibuti, namely C.fibrillososalor, C.pseudosalor, and C.subtropicus are described as new to science based on morphological and phylogenetic evidences. Cortinariuspseudosalor is extremely morphologically similar to C.salor, but it differs from the latter by smaller coarsely verrucose basidiospores. Cortinariusfibrillososalor can be easily differentiated by its fibrillose pileus. The pileus of C.subtropicus becomes brown without lilac tint at maturity comparing with other members of section Delibuti. A combined dataset of ITS and LSU sequences was used for phylogenetic analysis. The phylogenetic reconstruction of section Delibuti revealed that these three new species clustered and formed independent lineages with full support respectively. A key to the three new species and related species of section Delibuti is provided in this work.

High expression of autophagy-related gene EIF4EBP1 could promote tamoxifen resistance and predict poor prognosis in breast cancer.

BACKGROUND: Breast cancer (BC) remains a public health problem. Tamoxifen (TAM) resistance has caused great difficulties for treatment of BC patients. Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) plays critical roles in the tumorigenesis and progression of BC. However, the expression and mechanism of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients are still unclear. AIM: To investigate the expression and functions of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients. METHODS: High-throughput sequencing data of breast tumors were downloaded from the Gene Expression Omnibus database. Differential gene expression analysis identified EIF4EBP1 to be significantly upregulated in cancer tissues. Its prognostic value was analyzed. The biological function and related pathways of EIF4EBP1 was analyzed. Subsequently, the expression of EIF4EBP1 was determined by real-time reverse transcription polymerase chain reaction and western blotting. Cell Counting Kit-8 assays, colony formation assay and wound healing assay were used to understand the phenotypes of function of EIF4EBP1. RESULTS: EIF4EBP1 was upregulated in the TAM-resistant cells, and EIF4EBP1 was related to the prognosis of BC patients. Gene Set Enrichment Analysis showed that EIF4EBP1 might be involved in Hedgehog signaling pathways. Decreasing the expression of EIF4EBP1 could reverse TAM resistance, whereas overexpression of EIF4EBP1 promoted TAM resistance. CONCLUSION: This study indicated that EIF4EBP1 was overexpressed in the BC and TAM-resistant cell line, which increased cell proliferation, invasion, migration and TAM resistance in BC cells.

Five new species of Inosperma from China: Morphological characteristics, phylogenetic analyses, and toxin detection.

Many species of Inosperma cause neurotoxic poisoning in humans after consumption around the world. However, the toxic species of Inosperma and its toxin content remain unclear. In the present study, we proposed five new Inosperma species from China, namely, I. longisporum, I. nivalellum, I. sphaerobulbosum, I. squamulosobrunneum, and I. squamulosohinnuleum. Morphological and molecular phylogenetic analyses based on three genes (ITS, nrLSU, rpb2) revealed that these taxa are independent species. A key to 17 species of Inosperma in China is provided. In addition, targeted screening for the most notorious mushroom neurotoxins, muscarine, psilocybin, ibotenic acid, and muscimol, in these five new species was performed by using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Our results show that the neurotoxin contents in these five species varied: I. sphaerobulbosum contains none of the tested neurotoxins; I. nivalellum is muscarine positive; I. longisporum and I. squamulosohinnuleum contain both ibotenic acid and muscimol, and I. squamulosobrunneum only contains muscimol; psilocybin was not detected in these five new species.

Two new phenolic glycosides from the fruits of Illicium verum.

Two new phenolic glycosides (1-2) and eleven known compounds (3-13) were isolated from the fruits of Illicium verum Hook.f. using silica-gel column and preparative middle pressure liquid chromatography (MPLC). The structures of the compounds were elucidated by NMR spectroscopic data. Among them, compounds 3, 5, and 10 were isolated from the family Magnoliaceae for the first time. Additionally, all the compounds were evaluated for their anti-complementary activities against the classical pathway (CP) and the alternative pathway (AP).

Development of a method to screen and isolate xanthine oxidase inhibitors from black bean in a single step: Hyphenation of semipreparative liquid chromatography and stepwise flow rate countercurrent chromatography.

Black bean, in which isoflavones are the main active constituent, also contains saponins and monoterpenes. Soybean isoflavone is a secondary metabolite that is formed during the growth of soybean; it exhibits antioxidant and cardiovascular activities and traces estrogen-like effects. In this study, black bean isoflavones were extracted with n-butanol, and ultrafiltration-liquid chromatography-mass spectrometry was used to screen their activity. Subsequently, the inhibitors were isolated and purified using semipreparative liquid chromatography and stepwise flow rate countercurrent chromatography. Thereafter, five active compounds were identified using mass spectrometry and nuclear magnetic resonance experiments. Finally, the inhibition types of the xanthine oxidase inhibitors were determined using enzymatic kinetic studies. The IC50 values of daidzin, glycitein-7-O-glucoside, genistin, daidzein, and genistein were determined to be 35.08, 56.22, 30.76, 68.79, and 95.37 µg/mL, respectively. Daidzin, genistin, and daidzein exhibited reversible inhibition, whereas glycitein-7-O-glucoside and genistein presented irreversible inhibition. This novel approach, which was based on ultrafiltration-liquid chromatography-mass spectrometry and stepwise flow rate countercurrent chromatography, is a powerful method for screening and isolating xanthine oxidase inhibitors from complex matrices. The study of enzyme inhibition types is helpful for understanding the underlying inhibition mechanism. Therefore, a beneficial platform was developed for the large-scale production of bioactive and nutraceutical ingredients.

Two new toxic yellow Inocybe species from China: morphological characteristics, phylogenetic analyses and toxin detection.

Some species of Inocybe s. str. caused neurotoxic poisoning after consumption around the world. However, there are a large number of species in this genus that have not been studied for their toxicity or toxin content. In this study, we report two new toxic yellow Inocybe s. str. species from China based on morphological characteristics, phylogenetic analyses and toxin detection. Among the two species, Inocybesquarrosolutea is reported as a newly recorded species of China. We also describe a new species, I.squarrosofulva, which is morphologically similar to I.squarrosolutea. The new species is characterized by its ochraceous squarrose pileus, distinctly annulate cortina on the stipe, nodulose basidiospores and thick-walled pleurocystidia. Muscarine in the fruitbodies was detected by UPLC-MS/MS, the content in I.squarrosolutea and I.squarrosofulva were 136.4 ± 25.4 to 1683.0 ± 313 mg/kg dry weight and 31.2 ± 5.8 to 101.8 ± 18.9 mg/kg dry weight, respectively.

Trimethylamine N-Oxide Metabolites in Early Pregnancy and Risk of Gestational Diabetes: A Nested Case-Control Study.

OBJECTIVES: This study aimed to investigate the associations between trimethylamine N-oxide (TMAO) and related metabolites in early pregnancy and the risk of gestational diabetes mellitus (GDM). DESIGN: A prospective cohort of 22,302 pregnant women from 2010 to 2012 in Tianjin, China, was used to perform a nested case-control study. A total of 243 women with GDM and 243 women without GDM matched by maternal age (±1 year) were used as cases and controls, respectively. Conditional logistic regression and restricted cubic spline were used to examine the full-range risk associations between individual TMAOs metabolites at the first antenatal care visit with GDM. Trimethylamine conversion ratio (TMAR) was defined as trimethylamine (TMA)/its precursors, and trimethylamine N-oxide conversion ratio (TMAOR) was defined as TMAO/TMA. An additive interaction between high TMAR and low TMAOR indicates a state of TMA accumulation, and a mathematical interaction between high TMAR and high TMAOR indicates accumulation of TMAO. RESULTS: TMA was linearly associated with GDM, whereas TMA precursors and TMAO were inversely associated with GDM with clear threshold effects, i.e., 16 nmol/mL for TMAO, 200 nmol/mL for betaine, 112 nmol/mL for l-carnitine, and 110 and 270 nmol/mL for cholinechloride (a U-shaped relationship). Copresence of TMAR >0.35 and TMAOR ≤0.15 was associated with a markedly higher OR (11.16; 95% CI, 5.45 to 22.8), compared with TMAR >0.35 only (OR = 1.71; 95% CI, 0.42 to 6.95) or TMAOR ≤0.15 only (OR = 2.06; 95% CI, 1.09 to 3.90), with a significant additive interaction. However, the mathematical interaction was nonsignificant. CONCLUSIONS: TMAO metabolites in the early pregnancy were associated with the risk of GDM, whereas TMA was more likely to play a causal role in GDM.

Plasma Levels of Amino Acids Related to Urea Cycle and Risk of Type 2 Diabetes Mellitus in Chinese Adults.

Objective: This study aimed to test associations between type 2 diabetes mellitus (T2DM) and metabolites in urea cycle including arginine, citrulline and ornithine. Methods:This study used a hospital-based cross-sectional study design. We retrieved medical notes of 401 in-patients with onset of T2DM within 2 years and 1,522 healthy subjects who attended annual physical examination. All cases were admitted to a tertiary care center in Jinzhou, China from May 2015 to August 2016. Binary logistic regression analyses were performed to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Results:Patients with T2DM had higher arginine, and lower ornithine than control subjects. Levels of citrulline were similar in two groups. Arginine was positively associated with T2DM (ORs: 1.20, 1.17-1.23) while ornithine was negatively associated with T2DM (OR: 0.89, 0.88-0.91). After adjustment for other amino acids and traditional risk factors, these associations were still significant and persistent for arginine and ornithine. The association between citrulline and T2DM was not significant. Their ratios of pairs of two amino acids were associated with increased risk of T2DM. After adjustment for other ratios of amino acids, effect size for T2DM remained significant. Further adjustment for traditional risk factors did not lead to large changes (ORs: 1.78, 1.20-2.65 for the ratio of arginine to ornithine; ORs: 1.59, 1.37-1.86 for the ratio of citrulline to ornithine, respectively) except the ratio of arginine to citrulline. Conclusions: Plasma levels of amino acids related to urea cycle and their ratios of these amino-acids were associated with T2DM in Chinese adults.

Comparison of the inhibition potential of parthenolide and micheliolide on various UDP-glucuronosyltransferase isoforms.

Parthenolide (PTL) and micheliolide (MCL) are sesquiterpene lactones with similar structures, and both of them have been reported to exhibit multiple biochemical and pharmacological activities. This study aims to investigate the inhibition of these two compounds on the activity of UDP-glucuronosyltransferases (UGTs). In vitro incubation mixture for recombinant UGTs-catalyzed glucuronidation metabolism of 4-methylumbelliferone (4-MU) was utilized to investigate the inhibition potential. Inhibition kinetics (including inhibition type and parameters) were determined, and in silico docking was employed to elucidate the inhibition difference between PTL and MCL on UGT1A1. MCL showed no inhibition toward all the UGT isoforms, and PTL showed strong inhibition toward UGT1A1. The half-maximal inhibitory concentration (IC50) of PTL on the activity of UGT1A1 was determined to be 64.4 µM. Inhibition kinetics determination showed that PTL exerted noncompetitive inhibition toward UGT1A1, and the inhibition kinetic constant (Ki) was determined to be 12.1 µM. In silico docking method has been employed to show that hydrogen bonds between PTL and the activity cavity of UGT1A1 contributed to the stronger inhibition of PTL on the activity of UGT1A1 than MCL. In conclusion, PTL can more easily induce drug-drug interaction (DDI) with clinical drugs mainly undergoing UGT1A1-catalyzed glucuronidation.

Plasma tyrosine and its interaction with low high-density lipoprotein cholesterol and the risk of type 2 diabetes mellitus in Chinese.

AIMS/INTRODUCTION: Metabolomic markers have the potential to improve the predicting accuracy of existing risk scores for type 2 diabetes mellitus. The present study aimed to test the associations between plasma tyrosine and type 2 diabetes mellitus with special attention to identifying possible cut-off points for type 2 diabetes mellitus, and its interactive effects with low high-density lipoprotein cholesterol (HDL-C) and/or high triglyceride for type 2 diabetes mellitus. METHODS: From 27 May 2015 to 3 August 2016, we retrieved the medical notes of 1,898 inpatients with type 2 diabetes mellitus as the cases, and 1,522 individuals without diabetes as the controls who attended annual medical checkups from the same tertiary care center in Jinzhou, China. Logistic regression analyses were carried out to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic spline analysis nested in the logistic regression analysis was used to identify possible cut-off points of tyrosine for type 2 diabetes mellitus. The additive interaction was used to estimate interactions between high tyrosine and low HDL-C in type 2 diabetes mellitus patients. RESULTS: The OR of tyrosine for type 2 diabetes mellitus did not increase until 46 µmol/L and after that point, the OR rapidly rose with increasing tyrosine in a nearly linear manner. If 46 µmol/L was used to define high tyrosine, high tyrosine was associated with an increased OR of type 2 diabetes mellitus (adjusted OR 1.88, 95% CI 1.44-2.45). The presence of low HDL-C greatly enhanced the ORs of tyrosine for type 2 diabetes mellitus from 1.11 (95% CI 0.82-1.51) to 54.11 (95% CI 33.96-86.22) with significant additive interaction. CONCLUSIONS: In Chinese adults, tyrosine >46 µmol/L was associated with increased odds of type 2 diabetes mellitus, which was contingent on low HDL-C.

Hydroxy metabolites of polychlorinated biphenyls (OH-PCBs) exhibit inhibitory effects on UDP-glucuronosyltransferases (UGTs).

Hydroxy metabolites of polychlorinated biphenyls (OH-PCBs) are important substance basis for the toxicity of PCBs. This study aims to investigate the inhibition of OH-PCBs on the activity of UDP-glucuronosyltransferases (UGTs), trying to elucidate the toxicity mechanism of PCBs from a new perspective. In vitrohuman recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was used as the probe reaction. The number of chlorine atom can affect the inhibition potential of OH-PCBs towards different isoforms of UGTs, and complex structure-activity relationship was found for the inhibition of OH-PCBs on the activities of UGT isoforms. For the inhibition kinetic determination, 2'OHPCB106 and 4'OHPCB106 were selected as the representative OH-PCBs, and UGT1A1, 1A7, and 2B7 were chosen as the representative UGT isoforms. Competitive inhibition of 2'OHPCB106 and 4'OHPCB106 on the activities of UGT1A1, UGT1A7, and UGT2B7 was found. For 2'OHPCB106, the inhibition kinetic parameters (Ki) were calculated to be 0.4 µM for UGT1A1, 1.3 µM for UGT1A7, and 2.7 µM for UGT2B7, respectively. For 4'OHPCB106, Ki values were calculated to be 0.7 µM for UGT1A1, 6.8 µM for UGT1A7, and 4.8 µM for UGT2B7, respectively. In silico docking method was utilized to elucidate the inhibition difference of UGT1A1 by four OH-PCBs with similar structures (4'OHPCB9, 4'OHPCB26, 4'OHPCB112 and 4'OHPCB165). In conclusion, these data will be helpful for understanding the toxicity mechanisms of PCBs from a view of metabolic interference.

Bile acid metabolites in early pregnancy and risk of gestational diabetes in Chinese women: A nested case-control study.

BACKGROUND: Bile acid metabolism plays an important role in metabolism but it is uncertain whether bile acid metabolites in early pregnancy are associated with risk of gestational diabetes mellitus (GDM). METHODS: We organized a 1:1 case-control study nested in a prospective cohort of 22,302 pregnant women recruited from 2010 to 2012 in China: 243 women with GDM were matched with 243 non-GDM controls on age (±1 year). Conditional logistic regression and restricted cubic spline were used to examine full-range associations of bile acid metabolites with GDM. FINDINGS: All the 9 detectable bile acids were inversely associated with the risk of GDM, among them, 8 in nonlinear and one in largely linear manners in multivariable analysis. Glycoursodeoxycholic acid (GUDCA) at ≤0.07 nmol/mL and deoxycholic acid (DCA) at ≤0.28 nmol/mL had threshold effects and their decreasing levels below the cutoff points were associated with rapid rises in the risk of GDM. In traditional risk factor model, the stepwise procedure identified that GUDCA ≤ 0.07 nmol/mL and DCA ≤ 0.280 nmol/mL were still significant (OR: 6.84, 95%CI: 1.10-42.48 & 2.06, 1.26-3.37), while other bile acids were not. Inclusion of the two bile acids in the model increased the area under operating characteristic's curve from 0.69 to 0.76 (95% CI: 0.71-0.80) (P < .05). INTERPRETATION: Serum GUDCA ≤ 0.07 nmol/mL and DCA ≤ 0.28 nmol/mL in early pregnancy were independently associated with increased risk of GDM in Chinese pregnant women. FUNDING: Talent Recruitment Scheme grant of Tianjin Medical University and National Key Research and Development Program, etc.

New insights for risks of chlorophenols (CPs) exposure: Inhibition of UDP-glucuronosyltransferases (UGTs).

Chlorophenols (CPs) are important pollutants extensively utilized in industry, agriculture and forestry. The present study aims to determine the inhibition of CPs on the activity of the important phase II drug-metabolizing enzymes (DMEs) UDP-glucuronosyltransferases (UGTs). 100 µM of fourteen CPs were used for preliminary screening using in vitro incubation. Furthermore, half inhibition concentration (IC50) and inhibition kinetics were determined for CPs with significant inhibition towards UGT isoforms. In silico docking was used to explain the inhibition difference among CPs. Multiple UGT isoforms were inhibited by CPs. In silico docking showed that higher free binding energy due to hydrophobic interactions of 2.4-Dichlorophenol (2.4-DCP) or 4-Chloro-3-methylphenol (4C3MP) with UGT1A9 contributed to stronger inhibition potential of 2.4-Dichlorophenol (2.4-DCP) or 4-Chloro-3-methylphenol (4C3MP) towards UGT1A9 than 4-CP. Pentachlorophenol (PCP) was chosen as the representative CPs to determine the IC50 value towards UGT1A6, UGT1A9 and UGT2B7. IC50 was calculated to be 0.33 µM, 0.24 µM and 31.35 µM for the inhibition of PCP towards UGT1A6, UGT1A9 and UGT2B7. PCP was demonstrated to show competitive inhibition towards UGT1A6, UGT1A9 and UGT2B7, and the inhibition kinetic parameters (Ki) was calculated to be 0.18 µM, 0.01 µM and 5.37 µM for the inhibition of PCP towards UGT1A6, UGT1A9 and UGT2B7. All these information will be beneficial for elucidating the risk of CPs exposure from a new perspective.

Inhibition of UDP-glucuronosyltransferases (UGTs) by phthalate monoesters.

Phthalate monoesters are important metabolites of phthalate esters (PAEs) which have been extensively utilized in industry. This study aims to investigate the inhibition of phthalate monoesters on the activity of various isoforms of UDP-glucuronosyltransferases (UGTs), trying to elucidate the toxicity mechanism of environmental endocrine disruptors from the new perspectives. In vitro recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was employed to evaluate 8 kinds of phthalate monoesters on 11 sorts of main human UGT isoforms. 100 µM phthalate monoesters exhibited negligible inhibition towards the activity of UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A10, UGT2B4, UGT2B7, UGT2B15 and UGT2B17. The activity of UGT1A7 was strongly inhibited by monoethylhexyl phthalate (MEHP), but slightly inhibited by all the other phthalate monoesters. UGT1A9 was broadly inhibited by monobenzyl phthalate (MBZP), monocyclohexyl phthalate (MCHP), MEHP, monohexyl phthalate (MHP) and monooctyl phthalate (MOP), respectively. MEHP exhibited competitive inhibition towards UGT1A7, and MBZP, MCHP, MEHP, MHP and MOP showed competitive inhibition towards UGT1A9. The inhibition kinetic parameters (Ki) were calculated to be 11.25 µM for MEHP-UGT1A7, and 2.13, 0.09, 1.17, 7.47, 0.16 µM for MBZP-UGT1A9, MCHP-UGT1A9, MEHP-UGT1A9, MHP-UGT1A9, MOP-UGT1A9, respectively. Molecular docking indicated that both hydrogen bonds formation and hydrophobic interactions significantly contributed to the interaction between phthalate monoesters and UGT isoforms. All these information will be beneficial for understanding the adverse effects of PAEs.

15-Deoxy-Δ12,14-prostaglandin J2 alleviates hepatic ischemia-reperfusion injury in mice via inducing antioxidant response and inhibiting apoptosis and autophagy.

Hepatic ischemia-reperfusion (I/R) injury is a common clinical impairment that occurs in many circumstances and leads to poor prognosis. Both apoptosis and autophagy have been shown to contribute to cell death in hepatic I/R injury. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is one of the best-studied anti-inflammatory prostaglandins, which has been verified to exert anti-inflammatory and cell-protective functions in various types of cells and animal models. In this study we explored the effects of 15d-PGJ2 on both apoptosis and autophagy in mouse hepatic I/R injury and its possible mechanisms. A model of segmental (70%) hepatic warm ischemia was established in Balb/c mice, and the pathological changes in serum and liver tissues were detected at 6, 12, and 24 h post-surgery, while 15d-PGJ2 (2.5, 7.5, 15 µg, iv) was administered 30 min prior the surgery. Pretreatment with 15d-PGJ2 (7.5, 15 µg) significantly ameliorated I/R-induced hepatic injury evidenced by dose-dependent reduction of serum ALT and AST levels as well as alleviated tissue damages. 15d-PGJ2 pretreatment significantly decreased the serum TNF-α and IL-1ß levels and the hepatic expression of F4/80, a major biomarker of macrophages. 15d-PGJ2 pretreatment upregulated the Bcl-2/Bax ratio, thus reducing the number of apoptotic cells in the livers. 15d-PGJ2 pretreatment considerably suppressed the expression of Beclin-1 and LC3, thus decreasing the number of autophagosomes in the livers. Furthermore, 15d-PGJ2 pretreatment activated Nrf2 and inhibited a ROS/HIF1α/BNIP3 pathway in the livers. Pretreatment with the PPARγ receptor blocker GW9662 (2 µg, ip) partly reversed the protective effects of 15d-PGJ2 on hepatic I/R injury. In conclusion, our results confirm the protective effect of 15d-PGJ2 on hepatic I/R injury, an effect that may rely on a reduction in the activation of Kupffer cells and on activation of the Nrf2 pathway, which lead to inhibition of ROS generation, apoptosis, and autophagy.

[Synthesis and antioxidative activity of flavone derivatives containing 1,2,4-triazole structure].

Using bioactive compounds 7-hydroxy flavone, salicylaldehyde, cinnamic acid and 4-amino-5- mercapto-1,2,4-triazoles as starting materials, three new types of flavone derivatives containing 1,2,4-triazole structure were synthesized via different step reactions. These new compounds were characterized by 1IHNMR, ESI-MS, IR and elemental analysis. Their scavenging effects on the superoxide radical (O2·-), hydroxyl radical (·OH), DPPH · radical and their total reduction activities were tested. The results showed that all of the compounds possessed some antioxidative activity at the concentration of 0.5 mg · mL(-1), but the scavenging ability of the target compounds was lower than that of the standard compound Vc.

Disruption of the baculovirus core gene ac78 results in decreased production of multiple nucleocapsid-enveloped occlusion-derived virions and the failure of primary infection in vivo.

The Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ac78 gene is one of the baculovirus core genes. Recent studies showed that ac78 is essential for budded virion (BV) production and the embedding of occlusion-derived virion (ODV) into occlusion body during the AcMNPV life cycle. Here, we report that an ac78-knockout AcMNPV (vAc78KO) constructed in this study had different phenotypes than those described in the previous studies. A few infectious BVs were detected using titer assays, immunoblot analyses and plaque assays, indicating that ac78 is not essential for BV formation. Electron microscopy confirmed that the ac78 deletion did not affect nucleocapsid assembly and ODV formation. However, the numbers of multiple nucleocapsid-enveloped ODVs and ODV-embedded occlusion bodies were significantly decreased. Subsequently, the highly conserved amino acid residues 2-25 and 64-88 of Ac78, which are homologous to an oxidoreductase and cytochrome c oxidase, respectively, were demonstrated to play a crucial role in the morphogenesis of multiple nucleocapsid-enveloped ODV. Immunoblot analysis found that Ac78 was an ODV envelope-associated protein. Consistently, amino acid residues 56-93 of Ac78 were identified as an inner nuclear membrane sorting motif, which may direct the localization of Ac78 to the ODV envelope. In vivo infectivity assays showed that the occlusion bodies of vAc78KO were unable to establish primary infection in the midgut of Trichoplusia ni larvae. Taken together, our results suggest that ac78 plays an important role in BV production and proper multiple nucleocapsid-enveloped ODV formation, as well as AcMNPV primary infection in vivo.

[Pathologic changes of the palatopharyngeal muscles in patients with obstructive sleep apnea hypopnea syndrome of different degrees].

OBJECTIVE: To study the pathologic changes of the palatopharyngeal muscles with transmission electronmicroscopy (TEM) in patients with obstructive sleep apnea hypopnea syndrome (OSAHS), the role of the above muscle in OSAHS pathogenesis was discussed. METHODS: Thirty-eight palatopharyngeal muscle from OSAHS patients receiving uvulopalatopharyngoplasty (UPPP) were collected in in-patient department of Chinese Medical University and five palatal tumor patients receiving resection without snoring were chosen as the control. The palatopharyngeal muscle fiber and the feature of changes in mitochondrial morphology were observed by TEM. RESULTS: The pathological changes were not observed in the normal control group. The muscle fibers were regularly arranged, and the mitochondrial between muscles were normal. The palatopharyngeal myofibrillar in mild OSAHS group was regularly arranged. The Z lines were straight, and most mitochondria structure were normal. In the moderate group, the myofibrillar was disorganized, and the Z lines were shortened or distorted. The myofibrillar in severe group was disorganized, similar to point-like or flake, and the Z lines and the structures of sarcomeres were disappeared. And organelle were disintegrated and mitochondria were disappeared similar to flocculent. There existed obvious fatty infiltration in the palatopharyngeal muscle. In the control, mild, moderate and severe group, pharyngeal muscle fiber disarrangement of the occurrence rate was 0, 2/10, 8/13, 14/15, the occurrence rate of mitochondrial degeneration was 0, 2/10, 8/13, 14/15, increased with the severity of the ultrastructural changes in the trend of increasing incidence. CONCLUSIONS: The degree of OSAHS is correlated with the pathological changes of palatopharyngeal muscles. Incidence of myopathy is an important part of OSAHS secondary to chronic intermittent hypoxia in OSAHS and other pathological lesions, but also an important reason for increasing pharyngeal collapse.