Metformin-loaded lecithin nanoparticles induce colorectal cancer cytotoxicity via epigenetic modulation of noncoding RNAs

Background

Colorectal cancer (CRC) is major aliment around the word, with a cumulative rate of mortality. Metformin (MT) was recently approved as anticancer drug against solid tumors, such as CRC. Resistance to MT therapy remains to be a challenging matter facing the development of possible anti-cancer strategy. To circumvent this problem, MT nano-encapsulation has been introduced to sensitize resistant cancer cells. The purpose of the current study is to explore the MT's aptitude encapsulated in lecithin (LC) and chitosan (CS) nanoparticles to inhibit CRC proliferation through modulations of long noncoding RNAs (lncRNAs), micro RNAs (miRNAs), and some biochemical markers.

Methods and results

Cytotoxic screenings of the newly synthesized MT-based regimens; MT, MT-LC NPs (NP1), MT-CS NPs (NP2), and MT-LC-CS NPs (NP3) against colorectal cancerous Caco-2 and HCT116 cell lines versus normal WI-38 cells were performed. The epigenetic mechanistic effects of these proposed regimens on lncRNAs and miRNAs were investigated. Additionally, some protein levels were assessed in CRC cells upon treatments; YKL-40, PPARγ, E-cadherin (ECN), and VEGF. We resulted that NP1 recorded the highest significant cytotoxic effect on CRC cells. HCT116 cells were more sensitive to the NP1 compared to Caco-2 cells. Intriguingly, it was suggested that NP1 tackled the CRC cells through down-regulation of the H19, HOTTIP, HULC, LINC00641, miR-200, miR‐92a, miR-21, YKL-40, PPARγ, and VEGF expressions, as well as up-regulation of the miR-944 and ECN expressions.

Conclusions

We concluded that the NP1 can potentially be cytotoxic to CRC cells in-vitro by modulating noncoding RNA.

     

Raloxifene-encapsulated hyaluronic acid-decorated chitosan nanoparticles selectively induce apoptosis in lung cancer cells

Non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC) are leading causes of cancer mortality and morbidity around the world. Despite the recent advances in their diagnosis and therapy, their prognosis remains poor owing to the development of drug resistance and metastasis. Raloxifene (RX), a drug first used in the treatment of osteoporosis, was recently approved for NSCLC and HCC prevention. Unfortunately, many of the therapies that use RX are likely to become ineffective due to drug resistance. Herein, we developed a novel delivery strategy by utilizing hyaluronic acid (HA) and chitosan (CS) complexation to increase the half-life and activity of RX. Consequently, we explored the pro-apoptotic and cytotoxic effects of RX-HA-CS nanoparticles (NPs) against NSCLC (A549) and HCC (HepG2 and Huh-7) cell lines. The highest entrapment efficiency (EE%) was noted in RX-HA-CS NPs (92%) compared to RX-HA NPs (87.5%) and RX-CS NPs (68%). In addition, RX-HA-CS NPs induced the highest cytotoxicity against A549 cells compared to other platforms. The significant suppression of A549 cell viability was achieved via glucose uptake reduction resulting in diminished bioenergetics of cancer cells and activation of apoptosis via nitric oxide level elevation. This study is the first to assess the efficacy of RX in its HA-CS nano-formulation against lung and liver cancer cells and demonstrated its selective cytotoxic and apoptotic potential against human lung A549 cancer cell line. These findings demonstrate a promising drug delivery system to help mitigate drug resistance in lung cancer.     

Augmentation and evaluation of a parasitoid,Encarsia inaron,and a predator,Clitostethus arcuatus,for biological control of the pomegranate whitefly,Siphoninus phillyreae

The aim of this study was to evaluate the biological control potential of Encarsia inaron (Walker) (Hymenoptera: Aphelinidae) and a predator Clitostethus arcuatus (Rossi) (Coleoptera: Coccinellidae) against the pomegranate whitefly, Siphoninus phillyreae (Haliday) (Homoptera: Aleyrodidae) on pomegranate (Punica granatum L.) by mass rearing and augmentative releases of these two natural enemies during a long-term field study in Egypt. A study was conducted to evaluate the biological control potential of this pest by augmentation with a parasitoid, En. inaron, and a predator, C. arcuatus. Both species were mass reared and monthly releases were made in fields of pomegranate during each of 11 consecutive years (1996–2006). About 1,155,000 En. inaron and 990,000 C. arcuatus were released in fields in Assuit governorate in Egypt on pomegranate which was naturally infested by S. phillyreae. Populations of the natural enemies and parasitism were much higher in field plots where releases were made compared with where no releases were made. The maximum rate of parasitism reached 93% (88% by En. inaron) in the field treatment where releases were made, while parasitism peaked at 36% where no releases were made. The population of En. inaron was significantly correlated with the population of whitefly during the field season. Additional parasitism was by natural infestation with Eretmocerus parasiphonini Evans and Abd-Rabou (Hyneoptera: Aphelinidae). Among all years, the maximum number of C. arcuatus ranged from 13 to 44 beetles per 100 leaves for the treatment, and there were more predators in the release plot than in the control plot. These observations enhance understanding of the usefulness of these natural enemies after augmentation in the field.     

The potential impact of P53 and APO-1 genetic polymorphisms on hepatitis C genotype 4a susceptibility

The hepatitis C virus (HCV), the main cause of morbidity and mortality, is endemic worldwide. HCV causes cirrhosis and other complications that often lead to death. HCV is most common in underdeveloped nations, with the highest prevalence rates in Egypt. Tumor suppressor gene (P53) induces the expression of apoptotic antigen-1 gene (APO-1) by binding to its promoter for mediating apoptosis; an important mechanism for limiting viral replication. This study aims at investigating the impact of P53 72 Arg/Pro and APO-1 − 670 A/G polymorphisms on HCV genotype 4a susceptibility. Two hundred and forty volunteers were enrolled in this study and divided into two major groups; 160 HCV infected patient group and 80 healthy control group. HCV patients were classified according to Metavir scoring system into two subgroups; 72 patients in F0/1-HCV subgroup (patients with no or mild fibrotic stages) and 38 patients in F3/4-HCV subgroup (patients with advanced fibrotic stages). Quantification of HCV-RNA by qRT-PCR and fibrotic scores as well as genotyping of HCV-RNA, P53 at 72 Arg/Pro, and APO-1 at − 670 A/G were performed for all subjects. It was resulted that F0/1-HCV patients have significant differences of P53 at 72 (Pro/Pro and Arg/Arg) genotypes and dominant/recessive genetic models as well as APO-1 − 670 A/A genotype and dominant genetic model as compared to F3/4-HCV patients. Moreover, HCV patients have significant differences of P53 at 72 (Pro/Pro) genotype and recessive genetic model as well as APO-1 − 670 A/A genotype and dominant genetic model as compared to those of healthy individuals. Finally, it was concluded that P53 rs 1042522 (Pro/Pro and Arg/Arg) genotypes and APO-1 rs 1800682 A/A genotype may be potentially used as sensitive genetic markers for HCV genotype 4a susceptibility.     

Parasitoids as a bioagent to eliminate the insecticides to control the main pests-infested economic crops

Hemipterous insects are one of the important pests that attack different economic plants. A study was conducted to evaluate the biological control potential of these pests by augmentation with parasitoids, such as Microterys flavus (Howard), Metaphycus lounsburyi Howard (Encyrtidae), Encarsia sophia (Girault and Dodd), Coccophagus scutellaris (Dalman), Aphytis melinus DeBach (Aphelinidae) and Aphidius ervi Haliday (Braconidae). All the species were mass reared and monthly releases were made in fields of citrus, olive, tomato, sugar cane, mango and squash during each of 11 consecutive years (1999–2009). About 5,830,000 individuals of M. flavus, M. lounsburyi, E. sophia, C. scutellaris, A. melinus and A. ervi were released in the fields of Gharbiya, Marsa Matrouh, Daqahlyia, Qena, Qalyubiya and Behira governorates in Egypt on citrus, olive, tomato, sugar cane, mango and squash which were naturally infested by Ceroplastes floridensis Comstock, Saissetia oleae (Olivier) (Coccidae), Bemisia tabaci (Gennadius) biotype Q (Aleyrodidae), Pulvinaria tenuivalvata (Newstead) (Coccidae), Aulacaspis tubercularis (Newstead) (Diaspididae) and Aphis craccivora Koch (Aphididae), respectively. Population of the parasitoids and parasitism increased in field plots where releases were made when compared with where no releases were made. The maximum rate of parasitism reached 61.4, 92.1, 45.7, 59, 91 and 55.2% in the field treatment where releases were made, while parasitism peaked at 8.2, 13.5, 6, 2, 16 and 17.5% where no releases were made. The populations of M. flavus, M. lounsburyi, E. sophia, C. scutellaris, A. melinus, A. ervi were significantly correlated with the populations of C. floridensis, S. oleae, B. tabaci, P. tenuivalvata, A. tubercularis and A. craccivora during the field seasons. Additional parasitism was caused by natural infestations of Metaphycus helvolus (Compere) and M. lounsburyi (Howard) (C. floridensis), Scutellista cyanea (Motschulsky) (S. oleae), Encarsia lutea (Masi) and Eretmocerus mundus (Mercet) (B. tabaci biotype Q), Encarsia citrina (Craw) (A. tubercularis) and Aphelinus demyaati Abd-Rabou (A. craccivora). These observations enhance the understanding of the usefulness of these parasitoids after augmentation in the field.     

REVISION OF THE GENUS APHYTIS (HYMENOPTERA: APHELINIDAE) WITH DESCRIPTIONS OF TWO NEW SPECIES FROM EGYPT

Abstract  The Egyptian species of the aphelinid genus Aphytis Howard are reviewed. Aphytis azai Abd-Rabou and Aphytis matruhi Abd-Rabou are described as new species from Egypt. Each species is briefly diagnosed and known information on hosts and distributed is given. A. azai sp. nov. is similar to A. melinus but different in the measurement of antennal segments. A. matruhi sp. nov. differs from A. lepidosaphes by the relative length of propodeum, metanotum and scutellum. A key to the Egyptian species of Aphytis is provided.     

埃及Aphytis黄蚜小蜂属记述附二新种描述（膜翅目：蚜小蜂科）

对埃及的黄蚜小蜂属进行了综述,并描述了2个新种,即Aphytis azai Abd—Rabou和Aphytis matruhi Abd—Rabou。文章对产自埃及的17个种做了简要描述,还提供了寄主和分布信息,以及埃及黄蚜小蜂属的分种检索表。新种A．azai sp．nov．与A．melinus相似,但区别在于触角节的大小。新种A．matruhi sp．nov．区别于A．lepidosaphes之处在于间节、后胸腹板以及小盾片的相对长度不同。     

Selenium Nanoparticles Induce the Chemo-Sensitivity of Fluorouracil Nanoparticles in Breast and Colon Cancer Cells

Drug resistance is a major challenge of breast and colon cancer therapies leading to treatment failure. The main objective of the current study is to investigate whether selenium nanoparticles (nano-Se) can induce the chemo-sensitivity of 5-fluorouracil (FU)-encapsulated poly (D, L-lactide-co-glycolide) nanoparticles (nano-FU) in breast and colon cancer cell lines. Nano-Se and nano-FU were synthesized and characterized, then applied individually or in combination upon MCF7, MDA-MB-231, HCT 116, and Caco-2 cancerous cell lines. Cytotoxicity, cellular glucose uptake, and apoptosis, as well as malondialdehyde (MDA), nitric oxide (NO), and zinc (Zn) levels, were investigated upon the different treatments. We have resulted that nano-FU induced cell death in MCF7 and Caco-2 more effectively than MDA-MB-231 and HCT 116 cell lines. Moreover, nano-FU plus nano-Se potentiate MCF7 and Caco-2 chemo-sensitivity were higher than MDA-MB-231 and HCT 116 cancerous cell lines. It is relevant to note that Se and FU nano-formulations inhibited cancer cell bioenergetics via glucose uptake slight blockage. Furthermore, nano-FU increased the levels of NO and MDA in media over cancer cells, while their combinations with nano-Se rebalance the redox status with Zn increment. We noticed that MCF7 cell line is sensitive, while MDA-MB-231 cell line is resistant to Se and nano-Se. This novel approach could be of great potential to enhance the chemo-sensitivity in breast and colon cancer cells.

     

Biological control of the leafminer,Liriomyza trifolii by introduction,releasing, evaluation of the parasitoids Diglyphus isaea and Dacnusa sibirica on vegetables crops in greenhouses in Egypt

Abstract

The serpentine leafminer, Liriomyza trifolii (Burgess) (Diptera: Agromyzidae), is one of the most serious pests of various floricultural and vegetable crops. The European strains of the parasitoids Diglyphus isaea (Walker) (Hymenoptera: Eulophidae) and Dacnusa sibirica Telenga (Hymenoptera: Braconidae) were imported from The Netherlands. A total of 90,000 of these parasitoids were reared and released on cucumber and tomato in greenhouses. The parasitism rates of D. sibirica reached maximum 11.6% and 7.2% in the 11th week from the releasing date, on cucumber and tomato, respectively. Also the parasitism rates of the European strain of D. isaea increased until it reached a maximum 2.1% and 1.4%, in the tenth week from the releasing date on cucumber and tomato, respectively. It is concluded that the parasitoids D. sibirica and the European strain of D. isaea can be established in Egypt.     

THE ROLE OF COCCOPHAGUS SCUTELLARIS (HYMENOPTERA: APHELINIDAE) IN THE BIOLOGICAL CONTROL OF SOFT SCALE INSECTS (HOMOPTERA: COCCIDAE) IN EGYPT

Abstract Coccophagus scutellaris (Dalman) is one of the specific parasitoids that attack soft scale insects in Egypt. In the present study, C. scutellaris was reared from 6 species of soft scale insects. These are Ceroplastes flori-densis Comstock, Coccus hesperidum L., Pulvinaria floccgera (Westwood), P. psidii Maskell, Saissetia coffeae (Walker) and S. oleae (Oliver). The abundance of C. scutellaris was monitored from July to Nov. 1999–2000 in five localities in Egypt, the Beni-Suef, Cairo, Giza, Gharbiya and the Northern coast. C. scutellaris is considered an effective parasitoid of S. coffeae and S. oleae with maximum parasitism rates reaching 26% and 22% in Nov. and Aug. 1999, respectively.