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Background: Although folate status is associated with cervical carcinogenesis, it is not clear whether folate deficiency is associated with risk of cervical intraepithelial neoplasia (CIN) progression and infection with high-risk human-papillomavirus (hrHPV).Objectives: To evaluate the associations of RBC and serum folate concentrations with prevalence of CIN grades and hrHPV infection, their interactions with prevalence of CIN grades, and RBC folate with the risk of CIN1 progressing to CIN2.Methods: Using data from the Shanxi CIN cohort of 2304 female Chinese adults, we used logistic-regression model to estimate ORs and prevalence ratios (PRs) of RBC and serum folate concentrations with prevalence of CIN grades and hrHPV infection. Categoric and spline analyses were used to evaluate the dose-response relations. We estimated the association of RBC folate with risk of CIN1 progressing to CIN2 in the nested case-control cohort.Results: An inverse association was observed between increased RBC folate concentration and the odds of all CIN grades [quartile 1 (Q1) compared with Q4: OR: 2.28; 95% CI: 1.77, 2.93; Ptrend < 0.001]. Significant interaction of RBC folate and hrHPV infection was observed for prevalence of CIN2 or above (Pinteraction < 0.01). No associations were found between RBC and serum folate with PRs of hrHPV in each CIN grade. Over a median follow-up of 21.0 mo, RBC folate was associated with increased risk of CIN1 progressing to CIN2 (Q1 compared with Q4: OR: 3.86; 95% CI: 1.01, 14.76).Conclusions: Our study indicates that RBC folate concentration is associated with prevalence of CIN grades and CIN1 progression in female Chinese adults. Maintenance of normal folate status is important for reducing the risk of CIN and its progression in women with or without hrHPV infection. [ABSTRACT FROM AUTHOR]

Abstract This work attempted to prolong the validity of the molybdate mixed solution and ascorbic acid solution used in the phosphomolybdenum blue spectrophotometric method by improving their preservation according to the influence factors. The results showed that the molybdate mixed solution can be directly preserved in darkness with validity over half a year. The ascorbic acid solution is influenced by light, temperature, pH, metal ions, oxygen, and bacteria. The validity of ascorbic acid is shortened as the temperature rises. Through keeping in darkness, adding complexing agents, adjusting pH, removing oxygen and sterilization, the validity of ascorbic acid solution was prolonged to over 2.7 times under 4 °C and over 5 times under 25 °C. At the same time, the hybrid solution of ascorbic acid solution and molybdate mixed solution should be preserved separately, otherwise the using effect is poor. Highlights • Meet the current development trend on long-term monitoring of phosphate • Improve the reagents preservation methods in phosphomolybdenum blue reaction • Prolong the validity of the molybdate mixed solution and ascorbic acid solution • Reduce the cost of the reagents replacement in the process of phosphate detection [ABSTRACT FROM AUTHOR]

Background: Although folate deficiency has long been implicated in cancer development, uncertainties remain concerning its role in cervical cancer prevention. In particular, the interaction between human papillomavirus (HPV) and folate in the risk of cervical intraepithelial neoplasia (CIN) has been little studied. Objective: The goal of this study was to evaluate the dose-response association of serum folate with the risk of CIN, and the potential for HPV to modify the risk of CIN. Design: We performed a cross-sectional analysis of screening data in 2304 women aged 19-65 y who participated in an ongoing cohort of 40,000 women in China. Both categoric and spline analyses were used to evaluate the dose-response relation between serum folate and CIN risk. Results: After adjusting for potential confounders, a statistically significant inverse association between serum folate concentration and at least grade 2 CIN (CIN2+) risk was observed (1st quartile compared with 4th quartile: OR = 1.40; 95% CI: 1.09, 1.79; P-trend < 0.01); however, serum folate concentration was not associated with CIN1 risk. The risk patterns are similar when limited to only CIN2 and CIN3. An inverse linear relation between increased serum folate concentration and the risk of higher-grade CIN (CIN2, CIN3, and CIN2+) was also observed (for CIN2+: P-overall < 0.01, Pnonlinearity = 0.96). The highest risk of CIN2+ was observed in women with high-risk HPV types, who also had the lowest serum folate concentrations (P-interaction < 0.01). Conclusions: Our study indicates that serum folate is inversely associated with the risk of higher-grade CIN in Chinese women either with or without high-risk HPV infection. Thus, maintenance of normal serum folate levels may prove important for reducing the risk of CIN in women. [ABSTRACT FROM AUTHOR]

Abstract Statistical analysis of rainfall data from 2005 to 2015 showed that atmospheric deposition supplied large amount of dissolved inorganic nitrogen (38–155 mg·m−2·month−1) in N-deficient South China Sea and Eastern Indian Ocean. To understand marine ecosystem responses to increasing nutrient disturbances, we implemented field mesocosm experiments to study phytoplankton community structure and biodiversity responses to nutrient treatments with nitrate, phosphate and iron across tropical seas. Our results showed that DIN supply would change phytoplankton community structure and stimulated the regime shift from cyanobacteria to diatoms (relative dominance R > 0). Phytoplankton communities were dominated by diatoms (relative abundance >50%) accompanied by high chlorophyll a content with 1.58–39.27 μg·L−1 in DIN-added cultures, whereas cyanobacteria dominated communities (relative abundance >60%) with low biomass of 0.12–0.18 μg·L−1 in undisturbed cultures. Simultaneously increased DIN loading from atmospheric deposition would decrease ecological diversity of tropical seas owing to species competition and succession (Shannon diversity H′ decreased to <1). Graphical abstract Unlabelled Image Highlights • Wet deposition supplied large amount of DIN in two tropical seas. • Regime shift from cyanobacteria to diatoms was stimulated following DIN supply. • The study indicated that phytoplankton diversity of two tropical seas would be reduced following exogenous nutrients supply. • Management practices should be advocated to protect ecological diversity. [ABSTRACT FROM AUTHOR]

Natural QR (quinine oxidoreductase) inducers play critical roles in cancer chemoprevention. Because tea seed saponins of Camellia sinensis exhibited significant QR inducing activities, this study aimed to find bioactive theasaponin derivatives by structure modification on the sugar part and acyl groups. Three kinds of hydrolysis methods were employed to afford 7 major acid hydrolysis products ( 1 – 7 ), 10 alkaline hydrolysates ( 8 – 17 ) and 2 derivatives ( 3, 18 ) by oxidative alkaline-degradation. They were elucidated as kaempferol ( 1 ), camelliagenin B ( 2 ), camelliagenin A ( 3 ), 21- O -angeloybarringtogenol C ( 4 ), 5-hydroxymethylfurfural ( 5 ), 16- O -angeloybarringtogenol ( 6 ), 23-aldehyde-16- O -angeloybarringtogenol ( 7 ), desacyl-assamsaponin D ( 8 ), desacyl-theasaponin A 5 ( 9 ), desacyl-assamsaponin E ( 10 ), desacyl-theasaponin C 1 ( 11 ), desacyl-theasaponin E ( 12 ), desacyl-theasaponin E 13 ( 13 ), desacyl-assamsaponin F ( 14 ), desacyl-theasaponin F 1 ( 15 ), desacyl-theasaponin G ( 16 ), desacyl-assamsaponin A ( 17 ), camelliagenin C ( 18 ) accordingly. By the QR inducing activity assay, compounds 7, 12 and 14 were selected as potential QR inducing agents with IR value at 2.87, 3.02 and 2.33. [ABSTRACT FROM AUTHOR]

• A compact, low-cost, high sensitivity non-PM Sagnac-based interferometer was constructed. • The method of obtaining optimal interferometer fringe was proposed. • Standard A 0 modes were excited in aluminum sheets and detected by the interferometer. • B-Scan was utilized to inspect artificial defects on the surface of samples. Sagnac-based interferometers are promising devices for laser ultrasound (LU) inspection with the advantages of being robust, low-cost, and easy to integrate. Compared with all-Polarization Maintaining (all-PM) method, non-Polarization Maintaining (non-PM) method is more cost-effective and has greater compatibility, making it more practical in low-frequency ultrasound detection. The initial π/2 phase bias (IPB) and high fringe visibility are crucial for realizing the interferometer's full potential. However, a specific process of obtaining the optimal polarization control for non-PM configuration is still absent, leading to the unpredictable fringe states. In this paper, a novel and specific approach to obtaining optimal interference fringes for non-PM configuration based on the polarization control is proposed. Experimentally, the initial π/2 phase bias and 43.9% fringe visibility (50% is the highest in theory) were obtained. Guided waves of low-frequency A 0 mode in aluminum sheets were excited by a Q-switched pulse laser and detected by a non-PM Sagnac-based interferometer to inspect artificial defects on the surface of samples. Such a system provided a cost-effective non-contact detection scheme for out-of-plane Lamb wave which was very difficult to separate from LU signal with complex modes composition using conventional piezoceramics sensors. [ABSTRACT FROM AUTHOR]

In order to investigate the combined toxicities of copper nanoparticles (nano-Cu) with microplastic on microalgae Skeletonema costatum , growth inhibition tests were carried out. The toxic effects of copper nanoparticles and microplastic on the microalgae under singleness and coexistence conditions were investigated. Both copper nanoparticles and microplastic inhibited the growth of S. costatum. The growth inhibition ratio (IR) increased with the increasing of particle concentrations and incubation time. The toxicity of copper nanoparticles was reduced with the addition of microplastic. The concentrations of Cu2+ in the medium with or without addition of microplastic were determined. It was found that adsorption of Cu2+ on microplastic and aggregation between copper nanoparticles and microplastic are the main reasons for attenuation of toxicity of nano-Cu with adding microplastic. The adhesion and aggregate interactions between microalgae and nanomaterial were also approved by the observations through scanning electron microscopy. • Both nano-Cu and microplastic inhibited the growth of Skeletonema costatum. • Both nano-Cu and microplastic can be adsorbed by Skeletonema costatum. • Microplastic exposure alleviated the adverse effects of copper ion toxicity. • Microplastic reduced the toxicity of nano-Cu and copper ion through adsorption of a certain amount of copper ion. [ABSTRACT FROM AUTHOR]

Eight previously undescribed and 15 known components, including six neolignans, two monolignan, three sesquineolignans, three dineolignans, eight phenylpropanoids, and one steroid were identified from the seed testa of Vernicia fordii. Their structures were established based on the comprehensive analysis of NMR and ECD data. The anti-neuroinflammatory effects of the isolates were evaluated through nitrite assays in LPS-induced BV2 cells. As a result, isodiverniciasin A, diverniciasin B, diverniciasin C, isoprincepin, princepin, 3, 3′-bisdemethylpinoresinol, (+)-7-epi-sesamin-dicatechol, isoamericanin A, americanin B, 7 S , 8 R -americanin D, 4-hydroxyl cinnamic aldehyde, 3-hydroxyl-4-methoxyl cinnamic aldehyde and 24 R -6 β -hydroxy-24- ethylcholest-4-en-3-one exhibited significant inhibitory effects on nitric oxide (NO) production and isoprincepin, princepin, americanin B, and 4-hydroxyl cinnamic aldehyde suppressed the overexpression of inflammatory cytokines TNF-α, IL-1β, and IL-6 in over-activated microglia. The results suggested that bioactive ingredients from the seed testa of V. fordii can serve as potential therapeutic agents for neurodegenerative diseases. Twenty-three components, including eight undescribed ones, were identified from the seed testa of Vernicia fordii (Hemsl.) Airy Shaw (Euphorbiaceae). Some of the isolates showed anti-neuroinflammatory effects in activated microglia cells. Image 1 • Eight previously undescribed and fifteen known compounds were isolated from Vernicia fordii. • Twenty three compounds from Vernicia fordii showed inhibitory effects on nitric oxide production in over-activated microglial. • A plausible biosynthetic pathway was proposed. [ABSTRACT FROM AUTHOR]

A novel sample pretreatment strategy for separation and detection of atrazine from seawater was established with molecular imprinting solid-phase extraction (MISPE). Cyromazine was used as dummy-template based on computational analysis to synthesize dummy-template molecularly imprinted polymers (DMIPs) as sorbent of MISPE for atrazine analysis. The DMIPs were irregular loose porous layered structure characterized by scanning electron microscopy and showed higher binding capacity than non-imprinted polymers through adsorption experiments. An offline MISPE procedure using DMIPs as sorbent coupled with high-performance liquid chromatograph was developed for separation and purification of atrazine from seawater samples. The recoveries of atrazine in the spiked seawater samples ranged from 86.7% to 98.6%, and the relative standard deviation was less than 4.07% (n = 3) under optimal conditions indicating that the proposed method was suitable for the detection of trace residual atrazine in seawater. In addition, no atrazine was detected in three seawater samples from Jiaozhou bay, China. Unlabelled Image • Cyromazine was selected as dummy-template based on molecular simulation. • Dummy-template molecularly imprinted polymers (DMIPs) for atrazine was prepared. • The DMIPs were used as sorbent of molecular imprinting solid-phase extraction (MISPE). • An optimized MISPE procedure was developed to analyze atrazine in seawater from the Jiaozhou Bay, China. [ABSTRACT FROM AUTHOR]

We have previously documented that a cellular chaperone protein, FKBP52, which is phosphorylated at both tyrosine and serine/threonine residues, interacts with the D-sequence in the inverted terminal repeats of the adeno-associated virus 2 (AAV) genome, inhibits the viral second-strand DNA synthesis, and leads to inefficient transgene expression from recombinant AAV vectors in certain cell types (J. Virol., 75: 9818-9678, 2001). We have also demonstrated that FKBP52 is dephosphorylated at tyrosine residues by T cell protein tyrosine phosphatase (TC-PTP) (J. Virol. 77: 2741-2746, 2003). However, the identity of the putative serine/threonine protein phosphatase that dephosphorylates FKBP52 at serine/threonine residues has remained elusive. Using known inhibitors of serine/threonine kinases and phosphatases, we were able to rule out the involvement of MAP kinase, PK-A, PK-C, PK-G, MLC kinase, PI3 kinase, and PI4 kinases since none of these inhibitors had any effect on AAV-mediated transgene expression. Calyculin A and Cyclosporin A also had no effect. Thus, we ruled out the involvement of protein phosphatase 1 (PP1) and protein phosphatase 2B (PP2B) in AAV transduction. However, inhibition of protein phosphatase 2A (PP2A), and protein phosphatase 5 (PP5), resulted in a significant inhibition. These data suggested PP5 to be a candidate enzyme. PP5 is ubiquitously expressed in all mammalian tissue, and is localized predominantly in the nucleus. Recent studies have revealed that PP5 participates in the regulation of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) phosphorylation. Since DNA-PKcs has been implicated in AAV proviral integration, we hypothesized that FKBP52 is phosphorylated at serine/threonine residues by DNA-PKcs, and dephosphorylated by PP5, as depicted schematically in the model shown here.We systematically examined whether PP5 plays a role in the regulation of FKBP52 phosphorylation, and consequently, in AAV-mediated transgene expression. The transduction efficiency of AAV-EGFP vectors was decreased by ∼40% with pre-treatment of cells with okadaic acid (p<0.05), a known inhibitor of PP5, but no significant change was observed with pre-treatment low concentrations of fostriecin, known to inhibit PP2A (p>0.05). Deliberate over-expression of PP5 in 293 cells, which did not influence cellular growth, led to ∼5-fold increase in AAV transduction efficiency. We hypothesize that FKBP52 is a substrate for PP5, and suggest that PP5-mediated dephosphorylation of FKBP52 at serine/threonine residues can be exploited to augment the transduction efficiency of AAV vectors, which should have implications in the optimal use of these vectors in human gene therapy.Molecular Therapy (2006) 13, S1–S2; doi: 10.1016/j.ymthe.2006.08.013 [ABSTRACT FROM AUTHOR]

The transduction efficiency of AAV vectors varies greatly in different cells and tissues in vitro and in vivo. We have documented that a cellular protein, FKBP52, inhibits the viral second-strand DNA synthesis, and consequently, transgene expression (J. Virol., 75: 9818, 2001). FKBP52 is phosphorylated at tyrosine residues by epidermal growth factor receptor protein tyrosine kinase (EGFR-PTK), which inhibits AAV second-strand DNA synthesis by greater than 90% (J. Virol. 72: 9835, 1998; J. Virol., 75: 9818, 2001). Tyrosine-phosphorylated FKBP52 is dephosphorylated by T-cell protein tyrosine phosphatase (TC-PTP), which negatively regulates EGFR-PTK signaling, and leads to a significant increase in AAV transduction (J. Virol. 77: 2741, 2003). We have documented high-efficiency transduction of hepatocytes in TC-PTP-transgenic mice (Gene Ther., 11: 1165, 2004). We have also documented that intracellular trafficking of AAV from cytosol to nucleus is improved in hematopoietic cells from TC-PTP transgenic mice (Hum. Gene Ther., 15: 1207, 2004). In the present studies, we studied the role of EGFR-PTK signaling in AAV-mediated transgene expression. Consistent with our previous studies, less than 5% of HeLa cells were transduced by single-stranded (ss) AAV-EGFP vectors, and pretreatment of cells with Tyrphostin 23 (Tyr23), a specific inhibitor of EGFR-PTK, or stable expression of TC-PTP resulted in respectively ∼12-fold and ∼15-fold increase in AAV transduction. Although transduction by self-complementary (sc) AAV2-EGFP vectors was ∼8-fold higher compared with their ss counterparts, pretreatment with Tyr23 or stable expression of TC-PTP resulted in a further ∼10-fold increase in transduction. These data suggested that Tyr23 and TC-PTP affected other aspects of EGFR-PTK signaling involved in regulating vector transduction. We next examined whether Tyr23 or TC-PTP modulated the ubiquitin/proteasome pathway, both because proteasomes have been implicated in the regulation of EGFR endocytosis, and proteasome inhibitors have been shown to augment AAV transduction. Treatment of HeLa cells with MG132, a specific inhibitor of proteasome, resulted in respectively ∼6-fold and ∼8-fold increase in transduction efficiency of ss and scAAV vectors, However, neither a synergistic nor an additive effect was observed following pretreatment with MG132+Tyr23 or MG132+TC-PTP with either ss or scAAV vectors in HeLa cells. Similar results were obtained with murine fibroblast cell line NIH3T3, adult mouse hepatocyte cell line H2.35, and fetal mouse hepatocyte cell line FL83B. Taken together, these data indicate that complex interactions between EGFR-PTK signaling and ubiquitin/ proteasome pathway affect various aspects of intracellular trafficking and second-strand DNA synthesis of AAV vectors. A better understanding of these interactions is likely to be important in yielding new insights in the optimal use of recombinant AAV vectors in human gene therapy.Molecular Therapy (2006) 13, S3–S4; doi: 10.1016/j.ymthe.2006.08.018 [ABSTRACT FROM AUTHOR]

An abstract of the article "An Additional Role of Cellular FKBP52 in Recombinant Adeno-Associated Virus 2 Vector-Mediated Gene Transfer and Transgene Expression," by Weihong Zhao, Steven H. Larsen and Arun Srivastava is presented.

The American Joint Committee on Cancer (AJCC) made improvements for staging pancreatic neuroendocrine tumors (pNETs) in its 8th Edition; however, multicenter studies were not included. We collected multicenter datasets (n = 1,086, between 2004 and 2018) to validate the value of AJCC 8 and other coexisting staging systems through univariate and multivariate analysis for well-differentiated (G1/G2) pNETs. Compared to other coexisting staging systems, AJCC 7 only included 12 (1.1%) patients with stage III tumors. Patients with European Neuroendocrine Tumor Society (ENETS) stage IIB disease had a higher risk of death than patients with stage IIIA (hazard ratio [HR]: 4.376 vs. 4.322). For the modified ENETS staging system, patients with stage IIB disease had a higher risk of death than patients with stage III (HR: 6.078 vs. 5.341). According to AJCC 8, the proportions of patients with stage I, II, III, and IV were 25.7%, 40.3%, 23.6%, and 10.4%, respectively. As the stage advanced, the median survival time decreased (NA, 144.7, 100.8, 72.0 months, respectively), and the risk of death increased (HR: II = 3.145, III = 5.925, and IV = 8.762). These findings suggest that AJCC 8 had a more reasonable proportional distribution and the risk of death was better correlated with disease stage. [ABSTRACT FROM AUTHOR]

Folate deficiency has been long implicated in cancer development. Although the role of folate in preventing cervical cancer is still unclear, emerging evidence shows that microRNAs (miRs) have great influence on tumor cell migration and invasion. The purpose of this study was to conduct an integrated analysis of miR expression in squamous cell carcinoma tissues with adequate or deficient serum folate. Further, study conducted tissue validation and functional analysis of miRs to uncover novel pathogenic mechanisms on the role of folate in squamous cell carcinoma (SCC). miR expression profiles were obtained from five paired primary SCC tumors with sufficient or deficient serum folate levels through Affymetrix GeneChip microRNA 4.0. This was followed by an integrated bioinformatics analysis and expanded sample size to verify core miRs by molecular biological validation. HeLa and SiHa cells with different concentrations of folate were used to clarify the roles of miR-27a on cell proliferation, migration, and invasion. MiR-27a expression was measured by the quantitative real-time polymerase chain reaction. Cell counting proliferation, wound healing, and transwell invasion assays were used to determine cell survival, proliferation, migration, and invasion abilities, respectively. Our study found increasing miR-27a expression in serum of normal, high-grade squamous intraepithelial lesion (HSIL), and SCC tissues (in order of magnitude), which trend was negatively correlated with serum folate content. Further, there were significant differences in cellular miR-27a expression between 200 nM and 500 nM folate concentrations, with higher folate concentrations showing lower proliferation, migration, and invasion in SCC. Finally, miR-27a promoted proliferation and invasion in HeLa cells, whereas a miR-27a inhibitor blocked cell proliferation and invasion. There is a significant association between miR-27a expression and folate during cervical carcinoma progression. Therefore, miR-27a could be used as a new biomarker for SCC diagnosis and prediction, suggesting a new therapeutic strategy for SCC treatment. [ABSTRACT FROM AUTHOR]

Estrogen receptors (ERs) are the primary mediators of estrogen signaling, and play crucial roles in the reproduction and development of vertebrates. The full-length cDNA of Perinereis aibuhitensis estrogen receptor ( paER ) was cloned and characterized for the first time. The positions of the cysteine residues and the residues around them, which constitute two zinc finger motifs and a P-box, are conserved in both vertebrates and invertebrates. A phylogenetic analysis revealed that paER is an orthologue of ER in the polychaete Platynereis dumerilii. A tissue distribution analysis of paER mRNA showed that it is expressed in various tissues, including the body wall, head, esophageal gland, esophagus, stomach, and most strongly in the intestines. Its expression was also measured in P. aibuhitensis after exposure to 17β-estradiol (E2) for 48 h. The paER mRNA levels in the body wall were measured after 6, 12, 24, and 48 h in E2-exposed and control animals. However, no significant differences in paER expression were observed between them at any time point. This report describes the first molecular characterization of full-length paER and its tissue-specific expression in P. aibuhitensis . [ABSTRACT FROM AUTHOR]

Five chalcanes (( α ′ R )-2, α ′-dimethoxy-furano-[4″, 5′′: 3′, 4′] chalcane, ( α ′ R , βR )-2′, α ′, β -trimethoxy-furano-[4″, 5′′: 3′, 4′] chalcane, ( α ′ S , βR )-2′, α ′, β -trimethoxy-furano-[4″, 5′′: 3′, 4′] chalcane, ( α ′ R , βR )-2′, β -dimethoxy- α ′-hydroxyethoxy-furano-[4″, 5′′: 3′, 4′] chalcane, ( α ′ S , βR )-2′, β -dimethoxy- α ′-hydroxyethoxy-furano-[4″, 5′′: 3′, 4′] chalcane) and a flavonoid glycoside (3′, 7-dihydroxy-6-methoxy-4′, 5′-methylenedioxyisoflavone 6-O- β -D- glucopyranoside), together with 15 known components, were isolated from the leaves of Millettia pulchra (Benth) Kurzvar-laxior (Dunn) Z. Wei, a traditional Zhuang medicine. Their chemical structures were established by extensive analysis of NMR, mass spectrometry and ECD spectra. Furthermore compounds ( α ′ R , βR )-2′, β -dimethoxy- α ′-hydroxyethoxy-furano-[4″, 5′′: 3′, 4′] chalcane, ( α ′ S , βR )-2′, β -dimethoxy- α ′-hydroxyethoxy-furano-[4″, 5′′: 3′, 4′] chalcane, quercetin, methyl 2-O- β -D-glucopyranosylbenzoate, 6,7-dimethoxy-3′,4′-methylenedioxyisoflavone and lyoniresinol were suggested to be potential chemopreventive agents because of their significant activity in inducing NQO1 ([NAD(P)H quinine oxidoreductase 1], a phase II metabolism enzyme). [ABSTRACT FROM AUTHOR]

Natural NQO1 [NAD(P)H quinine oxidoreductase 1] inducing agents play a critical role in cancer chemoprevention. The expression of NQO1 is regulated by Michael reaction acceptors (MRAs) via the Keap1/Nrf2/ARE signaling pathway. The aims of this study were to identify and characterize novel effective chemopreventive agents from naturally occurring products. Using bioassay-guided isolation approaches 16 bioactive MRAs from Millettia pulchra Kurz var-laxior (Dunn) Z.Wei, also called Yulangsan as a famous Zhuang medicine. The structures were elucidated as chalcone ( 1 – 7 ), flavonone ( 8 – 14 ), flavanone ( 15 ) and isoflavan ( 16 ). Their electrophilic abilities and NQO1 inducing activity were assessed using GSH (glutathione) rapid screening, and in vitro cell-based (Hepa 1c1c7 cells) assay, respectively. Compounds 3 , 4 , 6 , 13 , and 14 showed to have NQO1 inducing activity. Among them, compounds 4 and 14 interact with NQO1 at Gly 149, Gly 150, Phe 106, Typ 105 and His 161, revealed by molecular docking studies. [ABSTRACT FROM AUTHOR]

In the present study, interleukin-22 (IL-22) from So-iny mullet ( Liza haematocheila ) was identified, and its tissue expression in both healthy and Streptococcus dysgalactiae -infected fish was examined. The full length cDNA sequence of mullet IL-22 was 1070 bp, containing an open reading frame of 555 bp. The deduced amino acid sequence shared high similarity (45.1–67.9%) with IL-22 from other fish species. Mullet IL-22 also contained an IL-10 family signature and four cysteine residues that were well conserved in other vertebrate IL-22 molecules. Mullet IL-22 mRNA was highly expressed in kidney, moderately expressed in liver and gut, and relatively weakly expressed in spleen, and its expression was significantly up-regulated in all the examined tissues following S. dysgalactiae infection. Furthermore, recombinant mullet IL-22 protein was shown to promote the expression of β-defensin in the four tissues and to increase the survival rate of the fish infected with S. dysgalactiae . Our results suggest mullet IL-22 plays an important role in the immune defense against bacterial infection and has the potential to be used to treat bacterial diseases in fish. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of this study was to investigate the role of hysteroscopic polypectomy with endometrial ablation in the management of tamoxifen-associated endometrial polyps in postmenopausal women with a more than 3-year follow-up period. Study design: The medical records of 76 postmenopausal patients on tamoxifen who were performed hysteroscopic polypectomy with endometrial ablation were evaluated more than 3 years after the procedure with recurrence of polyps, recurrent abnormal uterine bleeding and surgical re-intervention. Results: Average follow-up period was 74.91±20.84 months. No patient underwent hysterectomy, 7 of 76 patients had a surgical re-intervention representing a total of 90.8% avoidance of additional surgery during the follow-up period, and 4 patients had a recurrent endometrial polyp representing the recurrence rate was 5.3%. 3 of 41 patients with postmenopausal bleeding had a recurrent abnormal uterine bleeding representing symptomatic relief rate is 92.7%. The treatment failed in 7 patients who requested surgical re-intervention: 4 patients requested a repeat polypectomy and ablation, 1 patient requested a repeat ablation and 2 patients requested a repeat hysteroscopy with uterine adhesion. No malignant endometrial pathological result was found. Conclusions: For postmenopausal patients suffering from endometrial polyps associated with tamoxifen, hysteroscopic polypectomy with endometrial ablation continues to be proven as a safe and effective minimally invasive treatment method. The high rate of surgical re-intervention avoidance, great symptomatic relief and low recurrence rate are very encouraging for this technology. [Copyright &y& Elsevier]

Summary: Purpose: To assess the risk/benefit profiles of EGFR TKIs monotherapy using erlotinib or gefitinib in comparison with single-agent chemotherapy using third-generation cytotoxics (gemcitabine, vinorelbine, taxanes) as the first-line treatment for chemonaÏve patients with advanced non-small cell lung cancer (ANSCLC) and poor performance status (PS). Methods: A pooled analysis and systematic review was performed using trials identified through MEDLINE, EMBASE, Cochrane Library, and the Clinical-Trials.gov. Data were collected from randomized and non-randomized phase II or III clinical trials of EGFR TKIs monotherapy or single-agent chemotherapy using third-generation cytotoxics published before 3/1/2010, and the pooled estimates for efficacy and safety outcomes of interest were calculated. Results: Fifteen eligible trials (1425 patients) were selected from 323 studies that initially were identified. In 5 of the selected single-agent chemotherapy studies, the elderly were included together with poor PS patients. Outcomes from these studies still were employed for a thorough analysis. Targeting poor PS patients, we found that the pooled response rate (95% confidence interval) to EGFR TKIs for unselected population was 6% (3–8%), not substantially different from 9% (6–13%) reported by single-agent chemotherapy trials using third-generation cytotoxics. However, EGFR TKIs had better disease control rates with a pooled estimate of 40% (33–47%), significantly higher than 30% (20–41%) of the cytotoxics. Single-agent chemotherapy trials enrolling both elderly and poor PS patients had better results with the pooled response rate and the pooled disease control rate was 13% (11–16%) and 41% (36–46%) respectively. For safety information, despite both treatments were well-tolerated, the toxicity profile of EGFR TKIs was clearly more favorable than that reported by chemotherapy. The severe hematological adverse events related to EGFR TKIs treatment were rare. EGFR TKIs also tended to be more effective in improvement of symptoms or quality-of-life (QOL). Conclusion: Although, both of the treatments had low response rates, EGFR TKIs tended to be more effective in control of tumor progression, reduction of therapy-related toxicities, improvement of symptoms or quality-of-life in the first-line treatments of ANSCLC patients with poor PS. Moreover, our data also suggest that the elderly patients without selection carefully according their PS should be separated from this population. Further investigations with valid comparison groups are necessary. [Copyright &y& Elsevier]

Fibroblast growth factor receptor 4 (FGFR4), belonging to the receptor tyrosine kinase family, is involved in cancer initiation and progression. The FGFR4 Gly388Arg polymorphism in the transmembrane domain of the receptor was shown to contribute to genetic susceptibility to cancer but the results were inconsistent. We performed a meta-analysis using 12 eligible case-control studies with a total of 4892 patients and 3663 controls to summarise the data on the association between the FGFR4 Gly388Arg polymorphism and cancer risks. The overall odds ratio (OR) with a 95% confidence interval (CI) showed statistical association between the FGFR4 Gly388Arg polymorphism and cancer risks under homozygote comparison, allele contrast and the recessive genetic model. In the subgroup analysis by ethnicity, statistically significantly increased cancer risks were found among Asians for homozygote comparison (OR=1.43, 95% CI=1.13–1.80, P heterogeneity =0.24), allele contrast (OR=1.16, 95% CI=1.04–1.29, P heterogeneity =0.25) and the recessive genetic model (OR=1.47, 95% CI=1.19–1.81, P heterogeneity =0.15). In the subgroup analysis for different tumour types, Arg388 allele had an effect of increasing the risks of breast (homozygote comparison OR=1.57, 95% CI=1.04–2.37, P heterogeneity =0.83 and the recessive model OR=1.51, 95% CI=1.02–2.24, P heterogeneity =0.80) and prostate cancer (Gly/Arg versus Gly/Gly: OR=1.16, 95% CI=1.02–1.32, P heterogeneity =0.74; Arg versus Gly: OR=1.17, 95% CI=1.07–1.29, P heterogeneity =0.18 and the dominant model: OR=1.20, 95% CI=1.06–1.35, P heterogeneity =0.89). Our meta-analysis suggests that the FGFR4 Gly388Arg polymorphism most likely contributes to susceptibility to cancer, especially in Asians. Besides, the Arg388 allele might be associated with increased risks of breast and prostate cancer. [Copyright &y& Elsevier]

The small ubiquitin-like modifier (SUMO) pathway in eukaryotes is an essential biological process involving cellular processes, development and organelle biogenesis. In a sequential enzymatic action, Ubc9 is an important conjunction enzyme in the SUMO pathway. Although the Ubc9 has been found in vertebrates, its expression in crustaceans is little known. In this study, the Ubc9 was identified in the embryo and ovary of a freshwater prawn Macrobrachium nipponense for the first time and it was denoted as MnUbc9. Bioinformatics analyses showed that this gene encodes a protein of 161 amino acids with predicted molecular mass of 18.32kDa. Real-time quantitative PCR analyses demonstrated that the expression levels varied significantly in the developing embryo and ovary. In the embryo, the expression level of MnUbc9 was higher at the cleavage stage (CS) than at the blastula stage (BS), and reached even higher levels at the protozoea stage (PS) and the zoea stage (ZS). In the ovary, the MuUbc9 expression was low at the early stage, but reached the highest at the yolk granule stage (YG), and then abruptly declined at the maturation stage (MA). The differential expressions of MnUbc9 in the embryo and ovary suggest that MnUbc9 may play an important role in embryogenesis and oogenesis of M. nipponense. [Copyright &y& Elsevier]