To explore the effect of kaempferol on non-small cell lung cancer based on network pharmacology and molecular docking.

Non-small cell lung cancer (NSCLC) is a common pathological type of lung cancer, which has a serious impact on human life, health, psychology and life. At present, chemotherapy, targeted therapy and other methods commonly used in clinic are prone to drug resistance and toxic side effects. Natural extracts of traditional Chinese medicine (TCM) have attracted wide attention in cancer treatment because of their small toxic and side effects. Kaempferol is a flavonoid from natural plants, which has been proved to have anticancer properties in many cancers such as lung cancer, but the exact molecular mechanism is still unclear. Therefore, on the basis of in vitro experiments, we used network pharmacology and molecular docking methods to study the potential mechanism of kaempferol in the treatment of non-small cell lung cancer. The target of kaempferol was obtained from the public database (PharmMapper, Swiss target prediction), and the target of non-small cell lung cancer was obtained from the disease database (Genecards and TTD). At the same time, we collected gene chips GSE32863 and GSE75037 in conjunction with GEO database to obtain differential genes. By drawing Venn diagram, we get the intersection target of kaempferol and NSCLC. Through enrichment analysis, PI3K/AKT is identified as the possible key signal pathway. PIK3R1, AKT1, EGFR and IGF1R were selected as key targets by topological analysis and molecular docking, and the four key genes were further verified by analyzing the gene and protein expression of key targets. These findings provide a direction for further research of kaempferol in the treatment of NSCLC.

Target gene selection for RNAi-based biopesticides against the hawthorn spider mite, Amphitetranychus viennensis (Acari: Tetranychidae).

BACKGROUND: Recently, RNA interference (RNAi)-based biopesticide, a species-specific pest control alternative, has been deregulated and commercialized in the US and Canada. The hawthorn spider mite, Amphitetranychus viennensis Zacher, is a major pest for rosaceous plants, which has been controlled primarily by synthetic pesticides. To address the emerging resistance issues in A. viennensis, we initiated a project to develop RNAi-based biopesticides. RESULTS: In this study, we (i) developed a dietary RNAi system for A. viennensis using leaf disc, (ii) assessed the suitability of multiple control genes to distinguish sequence-specific silencing from non-specific effects within this RNAi system, and (iii) screened for the target gene candidates. As a result, ß-Glucuronidase (GUS), an enzyme derived from E. coli and a broadly used reporter for plants is the appropriate control for A. viennensis RNAi, while green fluorescent protein (GFP), is not suitable due to its significantly higher mortality than the other controls. For target gene screening, suppression was confirmed for all the candidates, including two housekeeping genes (Vacuolar-type H + -ATPase subunit A (V-ATPase A) and Glyceraldehyde 3-phosphate dehydrogenase, (GAPDH)), and three genes associated with development (ATP-dependent RNA Helicase DDX3Y (Belle), CREB-binding protein (CBP), and Farnesoic acid O-methyltransferase (FaMet)). Knocking down of V-ATPase A resulted in the highest mortality (~ 90%) and reduced fecundity (over 90%) than other candidates. As for the genes associated with development, suppression of Belle and CBP, led to approximately 65% mortality, as well as 86% and 40% reduction in fecundity, respectively. Silencing of FaMet, however, had negligible biological impacts on A. viennensis. CONCLUSION: The combined efforts not only establish an effective dsRNA delivery method, but also provide potential target genes for RNAi-based biopesticides against A. viennensis, a devastating invasive pest for fruit trees and woody ornamental plants throughout Asia and Europe. © 2023 Society of Chemical Industry.

HDAC3-mediated silencing of miR-451 decreases chemosensitivity of patients with metastatic castration-resistant prostate cancer by targeting NEDD9.

BACKGROUND: Treatment of metastatic castration-resistant prostate cancer (mCRPC) with docetaxel often fails due to the emergence of chemoresistance. Thus, restoring chemosensitivity to docetaxel-based therapies remains a challenge in mCRPC treatment. METHODS: microRNA (miR)-451 expression was measured in docetaxel-treated prostate cancer cells and tumor tissues by quantitative reverse-transcription polymerase chain reaction . Cell-counting kit 8 assay was performed to determine docetaxel chemoresistance. Neural-precursor-cell-expressed developmentally downregulated protein 9 (NEDD9) was identified as a novel target of miR-451 by dual-luciferase reporter system. Chromatin immunoprecipitation and co-immunoprecipitation assay were performed to confirm that histone deacetylase 3 (HDAC3)/Sp1 (a highly evolutionarily conserved transcription factor) interacted with the Sp1 binding sites in miR-451 promoter. RESULTS: miR-451 was found to be silenced in docetaxel-treated prostate cancer cells and mCRPC tissues. Low miR-451 expression was closely associated with a high Gleason score, high Eastern Cooperative Oncology Group performance status score, visceral metastasis and poor prognosis. Low expression of miR-451 was significantly correlated with short progression-free survival (PFS) and overall survival (OS) according to Kaplan-Meier analysis, and miR-451 was determined to be an independent poor prognostic factor for PFS and OS in mCRPC patients by univariate and multivariate Cox regression analyses. NEDD9 was identified as a new and functional target of miR-451. Restoration of NEDD9 partially reversed the effects of miR-451 on enhancing chemosensitivity of prostate cancer cells. HDAC3 was confirmed to be involved in silencing of miR-451 expression in prostate cancer cells. CONCLUSIONS: The current data revealed a new HDAC3/Sp1/miR-451/NEDD9 signaling axis that regulates the chemosensitivity of prostate cancer cells and represents a novel therapeutic target for chemosensitizing mCRPC.

Trans-regional migration of the beet armyworm, Spodoptera exigua (Lepidoptera: Noctuidae), in North-East Asia.

The beet armyworm, Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae), is a serious polyphagous insect pest worldwide. This species is known as a long-distance migrant, and previous studies on its migration have been mostly carried out in regions where it can overwinter. However, what pattern of seasonal migration this species exhibits in regions where it cannot overwinter (i.e., the 'summer breeding region') remains unknown. Here, we present data from 14-years of monitoring on a small remote island located in the center of the Bohai Strait, in northern China, by means of searchlight trapping and ovarian dissection. We found that the population size of this overseas migration varied significantly among years, with very large migrations in 2005, 2007, 2009, and 2014 that resulted in annual total catches of more than ten thousand individuals. In addition, nightly catches exhibited a significant inter-month variability, with the vast majority of S. exigua moths being trapped in August and September, (81.1 ± 3.6%), making S. exigua one of the most frequently encountered species in that period. The mean time from the earliest trap capture to the latest capture within a given year was 113 ± 22 d (range 57 d [2003] to 138 d [2008]). The sex ratio (females: males) was significantly less than 1:1 in each month, but the proportion of females showed an upward trend from June to October. The majority of trapped females in summer were mated (94.4 ± 10.7% in June, 80.0 ± 6.4% in July) and sexually mature (88.9 ± 11.1% in June, 61.8 ± 12.3% in July), suggesting the onset of mating and/or sexual maturation does not terminate the migration behavior in this species. These findings provide a good starting point for study of the trans-regional migration of S. exigua across different climate zones.

Fluorescence quenching and spectrophotometric methods for the determination of daunorubicin with meso-tera (4-sulphophenyl) porphyrin as probe.

In this work, a synthetic meso-tera (4-sulfophenyl) porphyrin (TPPS4) was used as a probe to determine daunorubicin (DNR) by fluorescence quenching and spectrophotometric methods. At pH 4.6 potassium acid phthalate-NaOH buffer solution, a 1:1 complex of DNR interacted with TPPS4 formed via the electrostatic attractions and hydrophobic interactions, thus resulted in TPPS4 fluorescence quenching and absorption spectra change. The maximum excitation wavelength (λex) and the maximum emission wavelength (λem) are 435 nm and 672 nm, respectively. The fluorescence quenching values (ΔF) are the good linear relationship to the concentration of DNR in the range of 0.8-6.0 mgL(-1). The method exhibits high sensitivity with the detection limit (3σ) being 27.0 ng mL(-1). Meanwhile, a decrease of absorbance is detected at 433 nm with the appearance of a new absorption peak at 420 nm. The optimum reaction conditions, influencing factors and the effect of coexisting substances have been investigated in our experiment. The results showed that the method had a good selectivity and could be applied to determine DNR in serum and urine samples. In addition, the combine ratio between DNR and TPPS4 was measured and the charge distribution before and after reaction was calculated by quantum chemistry calculation AM1 method. The type of fluorescence quenching was discussed by the absorption spectra change, Stern-Volmer plots and fluorescence lifetime determination.

Interaction of proteins with aluminum(III)-chlorophosphonazo III by resonance Rayleigh scattering method.

In weak acid medium, aluminum(III) can react with chlorophosphonazo III [CPA(III), H(8)L] to form a 1:1 coordination anion [Al(OH)(H(4)L)](2-). At the same time, proteins such as bovine serum albumin (BSA), lysozyme (Lyso) and human serum albumin (HSA) existed as large cations with positive charges, which further combined with [Al(OH)(H(4)L)](2-) to form a 1:4 chelate. This resulted in significant enhancement of resonance Rayleigh scattering (RRS), second-order scattering (SOS) and frequency doubling scattering (FDS). In this study, we investigated the interaction between [Al(OH)(H(4)L)](2-) and proteins, optimization of the reaction conditions and the spectral characteristics of RRS, SOS and FDS. The maximum RRS wavelengths of different protein systems were located at 357-370 nm. The maximum SOS and FDS wavelengths were located at 546 and 389 nm, respectively. The scattering intensities (ΔI) of the three methods were proportional to the concentration of the proteins, within certain ranges, and the detection limits of the most sensitive RRS method were 2.6-9.3 ng/mL. Moreover, the chelate reaction mechanism or the reasons for the enhancement of RRS were discussed through absorption spectra, fluorescence spectra and circular dichroism (CD) spectra.

Resonance Rayleigh scattering spectra of ion-association nanoparticles of [Co(4-[(5-chloro-2-pyridyl) azo]-1, 3-diaminobenzene)2]2+-sodium dodecyl benzene sulfonate system and its analytical application.

In pH 1.8-3.0 Britton-Robinson (BR) buffer solution, cobalt (II) reacts with 4-[(5-Chloro-2-pyridyl) azo]-1, 3-diaminobenzene (5-Cl-PADAB, L) to form a cationic chelate [CoL(2)](2+). When interacting with anionic surfactants (AS) such as sodium dodecyl benzene sulfonate (SDBS), sodium dodecyl sulfate (SDS) or sodium dodecyl sulfonate (SLS), the chelate can only react with SDBS to form ternary ion-association complexes ([CoL(2)][SDBS](2)). By virtue of the extrusion action of water and Van der Waals force, the hydrophobic ion-association complexes draw close to each other and further aggregate to form {[CoL(2)][SDBS](2)}(n) nanoparticles with an average diameter of 30 nm. As a result, resonance Rayleigh scattering (RRS) is enhanced greatly and new RRS spectra appear. Under the same conditions, both SDS and SLS exhibit no similar reactions and do not result in obvious change of RRS. Therefore, SDBS can be determined selectively by RRS method in the presence of SDS or SLS. The wavelength of 516 nm was chosen as a detection wavelength, the linear range and the detection limit (3sigma) are 0.05-6.0 microg mL(-1) and 0.015 microg mL(-1) for the determination of SDBS, respectively. The characteristics of RRS spectra of the [CoL(2)](2+)-SDBS system, the optimum conditions of the reaction and the influencing factors have been investigated. The effects of coexisting substances have been examined too, indicating a good selectivity of the method for the determination of SDBS. The method can be used for the determination of SDBS in waste water and river water samples, and the results are satisfactory compared with those of standard samples of SDBS. Based on the formation of {[CoL(2)][SDBS](2)}(n) nanoparticles, a sensitive, simple and rapid method has been developed for the determination of SDBS in environmental water samples using a RRS technique. Moreover, the reaction mechanism was discussed.

Fluorescence quenching method for the determination of bleomycins A5 and A2 with halofluorescein dyes.

In weak acidic medium, the anticancer antibiotics bleomycin A5 (BLMA5) and bleomycin A2 (BLMA2) bind with halofluorescein dyes, such as erythrosin (Ery), eosin Y (EY) and eosin B (EB), to form ion-association complexes, which causes fluorescence quenching of halofluorescein dyes. The quenching values (DeltaF) are directly in proportional to the concentrations of bleomycins over the range 0.09-2.5 microg/mL. Based on this, a fluorescence quenching method for the determination of BLMA5 and BLMA2 has been developed. The dynamic range is 0.12-2.5 microg/mL for the determination of BLMA5 and 0.09-2.0 microg/mL for BLMA2, with detection limits (3sigma) of 0.04 microg/mL for BLMA5, 0.03 microg/mL for BLMA2, respectively. It has been applied to determine the two antibiotics in human serum, urine and rabbit serum samples. The recovery is in the range 90-102%. In this work, the optimum reaction conditions and the spectral characteristics of the fluorescence are investigated. The reasons for fluorescence quenching are discussed, based on the fluorescence theory.

Resonance Rayleigh scattering spectra for studying the interaction of anthracycline antineoplastic antibiotics with some anionic surfactants and their analytical applications.

In pH 5.8 acidic medium, the anionic surfactants such as sodium dodecyl sulfate (SDS), sodium dodecyl benzene sulfonate (SDBS) or sodium dodecyl sulfonate (SLS) can react with anthracycline antibiotics such as epirubicin (EPI), daunorubicin (DNR) or mitoxantrone (MXT) to form ion-association complexes, which lead to a great enhancement of resonance Rayleigh scattering (RRS) intensity and appearances of new RRS spectra. The maximum RRS peaks are situated at 313 nm for SDS-DNR and SDS-EPI system, 296 nm for SDS-MXT system. The linear ranges and detection limits for EPI, DNR and MXT are 0.26-20.0, 0.25-20.0, 0.14-10.0 and 0.074, 0.078, 0.042 microgmL(-1), respectively. In this paper, the characteristics of the absorption, fluorescence and RRS spectra of the reaction products are studied as well as the optimum reaction conditions and analytical chemistry properties. A sensitive, simple and rapid RRS method for the determination of anthracycline anticancer antibiotics has been developed.

A highly sensitive resonance Rayleigh scattering method for the determination of bleomycinA5 and bleomycinA2 with some halofluorescein dyes.

In a weak acidic medium, bleomycinA(5) (BLMA(5)) and bleomycinA(2) (BLMA(2)) can react with halofluorescein dyes such as erythrosine (Ery), eosin Y (EY), eosin B (EB) and Rose Bengal (RB) by virtue of electrostatic attraction and hydrophobic force to form ion-association complexes, which can result in the large-scale enhancement of resonance Rayleigh scattering (RRS) and the appearance of new RRS spectra. The increments of scattering intensity (Delta I) were directly proportional to the concentrations of bleomycin (BLM) in certain ranges. The detection limits for BLMA(5) and BLMA(2) ranged from 0.017 to 0.062 microg ml(-1). The Ery system had the highest sensitivity and its detection limit (3sigma) was 0.017 microg ml(-1) for BLMA(5) and 0.018 microg ml(-1) for BLMA(2), respectively. Using Ery as a RRS probe, a new highly sensitive method for the determination of BLM anticancer drugs has been developed. It was applied in the determination of BLMA(5) and BLMA(2) in serum and urine samples. The recovery was from 99.0% to 103.0%. In this work, the RRS spectral characteristics of the binding products and the optimum conditions of the reaction were investigated. The mechanism of ion-association reaction and the reasons of enhancement of resonance light scattering were discussed.