Valproate modulates the activity of multidrug resistance efflux pumps, as a chemoresistance factor in gastric cancer cells.

BACKGROUND: Drug resistance is one of the most critical problems in gastric cancer therapy. This study was performed to investigate the valproic acid effects on the proliferation of sensitive and resistant cell lines of human gastric cancer, and to explore the mechanism of the agent on multi drug resistance and apoptosis genes. METHODS: The cytotoxicity effect of valproic acid on the EPG85.257 and EPG85.257RDB cells was assessed by the MTT assay, and the IC50 concentration was evaluated. Apoptosis, genotoxicity, and drug resistance pump activity were evaluated using comet assay, Real-time PCR, and flow cytometry, respectively. Cell proliferation was assayed using a scratch test. RESULTS: Dose-dependent toxicity was recorded after treatment of cells with valproic acid. Valproic acid represented a significant growth inhibition on EPG85.257 cells with IC50 values of 5.84 µM and 4.78 µM after 48 h and 72 h treatment, respectively. In contrast, the drug-resistant counterpart represented 8.7 µM and 7.02 µM IC50 values after the same treatment time. Valproic acid induced PTEN, Bcl2, P53, Bax, P21, and caspase3 expression in EPG85.257 cells, whereas p21, p53, PTEN, and ABCB1 were overexpressed in EPG5.257RDB. Valproic acid hindered cell migration in both cell lines (P < 0.01). Valproate genotoxicity was significantly higher in the parent cells than in their resistant EPG85.257RDB counterparts. Valproate led to a 62% reduction in the daunorubicin efflux of the MDR1 pump activity. CONCLUSIONS: Valproate can affect drug resistance in gastric cancer via a unique mechanism independent of MDR1 expression.

MiR-548k suppresses apoptosis in breast cancer cells by affecting PTEN/PI3K/AKT signaling pathway.

Breast cancer is the most aggressive and fatal form of cancer among women globally. Although the role of some miRNAs that are often dysregulated in breast cancer has been deciphered, the regulatory function of others still remains unknown. The current study was aimed at determining the biological role and underlying mechanism of miR-548k in breast cancer. In this study, the significant overexpression of miR-548k in breast cancer tissues compared to adjacent normal tissues was confirmed. Also, bioinformatics analysis indicated that PTEN, as a negative regulator of PI3K/AKT signaling pathway, was a potential target of miR-548k, and its expression was downregulated in breast cancer tissues rather than normal tissues. Furthermore, the ectopic increase of miR-548k decreased the expression of PTEN in breast cancer, suggesting that PTEN is one of the potential downstream targets of miR-548k. Besides, functional analysis was conducted to assess the capability of miR-548k to alter apoptosis along with the changed expression levels of miR-548k in breast cancer cells. Based on this investigation, forced increase of miR-548k disrupted programmed cell death in MCF-7 cells. Apart from this, in silico study of miR-548 family supported its association with the main components of PI3K/Akt signaling pathway, opening a prospective research area in cancer therapy. In brief, suppression of PTEN partly mediated by miR-548k diminished apoptosis and promoted cell proliferation through PI3K/Akt pathway in breast cancer, suggesting a novel therapeutic axis, miR-548k/PTEN/ PI3K/Akt, for treatment of breast cancer in the future.

Designed miR-19a/b sponge induces apoptosis in lung cancer cells through the PI3K-PTEN-Akt pathway regulation.

BACKGROUND: MicroRNAs (miRNAs) are one of the main factors in cancer development and can alter the activity of proto-oncogenic or tumor suppressor genes. The miR-17-92 cluster, which comprises miR-17, miR-18a, miR-19a/b, miR-20a, and miR-92a, has been identified as a biomarker in a variety of cancer types. Among them, miR-19a/b exerts an oncogenic effect by suppressing tumor suppressor genes, including PTEN and TP53INP1in numerous types of cancers, including NSCLC. An miRNA sponge is an mRNA with multiple repetitive sequences that prevents miRNAs from interacting with their targets, thereby inhibiting their action. METHODS AND RESULTS: In this study, we designed an miR-19a/b sponge plasmid and transfected it into A549 lung cancer cell lines and analyzed its effects on PTEN and TP53INP1 gene expression as the main miR-19a/b target and apoptosis rate in these cell lines. CONCLUSIONS: The findings revealed that miR-19a/b sponge significantly increased PTEN and TP53INP1 mRNA expression. The effect of the sponge on TP53INP1 was much greater than that on PTEN. This is because TP53INP1 is directly (sponge effect) and indirectly (AKT pathway is affected by the P53 gene) affected by this sponge. In addition, compared with the control group, the percentage of primary and secondary apoptosis increased significantly (P value < 0.0001).

Inhibition of miR-155 in MCF-7 breast cancer cell line by gold nanoparticles functionalized with antagomir and AS1411 aptamer.

MicroRNAs are key factors for many biological functions. These regulatory molecules affect various gene networks and involve the subsequent signaling pathways. Therefore, disrupting the expression of these molecules is associated with multiple anomalies in the cells and body. One of the most important related abnormalities is the incidence of cancer. Thus, targeting microRNAs (miRNAs) is an effective approach for cancer gene therapy. Various factors are used for this purpose, including the antagomir nucleotide structure. There are some obstacles in the delivery of nucleotide therapeutics to the target cells, however, the use of nanoparticles could partly overcome these defeciencies. On the other hand, targeted delivery of antagomirs using aptamers, reduces nonspecific effects on nontarget cells. Considering the above, in this study, we designed and fabricated a nanocarrier composed of gold nanoparticles (GNPs), antagomir-155, and nucleolin specific aptamer for breast cancer study and therapy. Here, GNPs were synthesized using citrate reduction and were modified by polyA sequences, AS1411 aptamer, and antagomir-155. Attachment of molecules were confirmed using gel electrophoresis, atomic force microscopy imaging and electrochemical test. The specific entry of modified nanoparticles was investigated by fluorescence microscopy. The efficacy of modified nanoparticles was evaluated using a quantitative polymerase chain reaction (q-PCR) for miR-155 and its target gene. Efficient and specific delivery of AuNP-Apt-anti-miR-155 to target cells was confirmed in comparison with the control cell. The q-PCR analysis showed not only a significant decrease in mir-155 levels but also an elevated TP53INP1 mRNA, direct target of miR-155. The proposed structure inhibits proliferation and stimulates apoptosis by increasing the expression of TP53INP1. Our results suggest that AuNP-Apt-anti-miR-155 could be a promising nano constructor for breast cancer treatment.

Naltrexone; as an efficient adjuvant in induction of Th1 immunity and protection against Fasciola hepatica infection.

Toxic effects of available therapeutics are major drawbacks for conventional management approaches in parasitic infections. Vaccines have provided a promising opportunity to obviate such unwanted complications. In present study, we examined immune augmenting capacities of an emerging adjuvant, Naltrexone, against Fasciola hepatica infection in BALB/c mice. Seventy BALB/c mice were divided into five experimental groups (14 mice per group) including 1- control (received PBS), 2- vaccine (immunized with F. hepatica E/S antigens), 3- Alum-vaccine (immunized with Alum adjuvant and E/S antigens), 4- NLT-vaccine (immunized with NLT adjuvant and E/S antigens), and 5- Alum-NLT-vaccine (immunized with mixed Alum-NLT adjuvant and E/S antigens). Lymphocyte stimulation index was assessed by MTT assay. Production of IFN-γ, IL-4, IgG2a and IgG1 was assessed by ELISA method. Results showed that NLT, either alone or in combination with alum, can induce immune response toward production of IFN-γ and IgG2a as representatives of Th1 immune response. Also, using this adjuvant in immunization experiment was associated with significantly high proliferative response of splenocytes/lymphocytes. Utilization of mixed Alum-NLT adjuvant revealed the highest protection rate (73.8%) in challenge test of mice infected with F. hepatica. These findings suggest the potential role of NLT as an effective adjuvant in induction of protective cellular and Th1 immune responses against fasciolosis.

Assessment of expression of interferon γ (IFN-G) gene and its antisense (IFNG-AS1) in breast cancer.

BACKGROUND: The role of long non-coding RNAs has been extensively appreciated in the contexts of cancer. Interferon γ-antisense RNA1 (IFNG-AS1) is an lncRNA located near to IFN-γ-encoding (IFNG) gene and regulates expression of IFNG in Th1 cells. METHODS: In the present study, we evaluated expression of IFNG and IFNG-AS1 in 108 breast samples including tumoral tissues and their adjacent non-cancerous tissues (ANCTs) using real-time PCR. IFNG-AS1 was significantly upregulated in tumoral tissues compared with ANCTs (expression ratio = 2.23, P = 0.03). RESULTS: Although the expression of IFNG was higher in tumoral tissues compared with ANCTs (relative expression = 1.89), it did not reach the level of significance (P = 0.07). IFNG expression was significantly higher in HER2-negative tumoral tissues compared with HER2-positive ones (P = 0.01) and in grade 1 samples compared with grade 2 ones (P = 0.03). No other significant difference was found in expressions of genes between other groups. CONCLUSION: Significant strong correlations were detected between expression of IFNG and IFNG-AS1 in both tumoral tissues and ANCTs. The present study provides evidences for participation of IFNG and IFNG-AS1 in the pathogenesis of breast cancer and warrants future studies to elaborate the underlying mechanism.

Cerium Oxide Nanoparticles Synthesis Using Alhagi Maurorum Leaf Extract and Evaluation of Their Cytotoxic Effect on Breast Cancer Cell Lines and Antibacterial Effects.

INTRODUCTION: Green synthesis offers a fast, simple, and economical method for producing metallic nanoparticles.The basis of this method is to obtain nanoparticles using natural materials, such as plants, fungi, and bacteria, instead of harmful and expensive chemical-reducing agents. In this study, CeO2NPs were produced using Alhagi maurorum extract, and their anticancer and antibacterial activities were evaluated. METHOD: Alhagi maurorum extract was prepared according to a previously described protocol, and CeO2NPs were synthesized from the salt of this extract. The resulting nanoparticles were characterized using Transmission electron microscopy (TEM), scanning electron microscope (SEM), and X-ray diffraction (XRD) techniques. The antibacterial and cytotoxic effects of the nanoparticles were measured by MIC, MBC, and MTT assays, respectively. The results were analyzed using one-way analysis of variance (ANOVA) using Prism software. RESULTS: The MTT assay on breast cancer cell lines showed that the cytotoxic effect of CeO2NPs on cell lines was concentration-dependent. In addition, this nanoparticle was more effective against Gram-positive bacteria. CONCLUSION: These nanoparticles can be used as cancer drug delivery systems with specific targeting at low concentrations in addition to anticancer treatments. It can also have biological and medicinal applications, such as natural food preservation and wound dressing.

In silico identification and in vitro evaluation of MRPS30-DT lncRNA and MRPS30 gene expression in breast cancer.

BACKGROUND: It has been reported that long non-coding RNAs (lncRNAs) can play important roles in a variety of biological processes and cancer regulatory networks, including breast cancer. AIMS: This study aimed to identify a novel upregulated lncRNA in breast cancer and its associated gene using bioinformatics analysis, and then evaluate their potential roles in breast cancer. METHODS AND RESULTS: Extensive in silico studies were performed using various bioinformatics databases and tools to identify a potential upregulated breast cancer-associated lncRNA and its co-expressed gene, and to predict their potential roles, functions, and interactions. The expression level of MRPS30-DT lncRNA and MRPS30 was assessed in both BC tissues and cell lines using qRT-PCR technology. MRPS30-DT lncRNA and MRPS30 were selected as target genes using bioinformatics analysis. We found that MRPS30-DT and MRPS30 were significantly overexpressed in BC tissues compared with normal tissues. Also, MRPS30 showed upregulation in all three BC cell lines compared with HDF. On the other hand, MRPS30-DT significantly increased in MDA-MB-231 compared with HDF. While the expression of MRPS30-DT was significantly dropped in the resistance cell line MCF/MX compared to HDF and MCF7. Moreover, bioinformatics analysis suggested that MRPS30-DT and MRPS30 may play a potential role in BC through their involvement in some cancer signaling pathways and processes, as well as through their interaction with TFs, genes, miRNAs, and proteins related to carcinogenesis. CONCLUSIONS: Overall, our findings showed the dysregulation of MRPS30-DT lncRNA and MRPS30 may provide clues for exploring new therapeutic targets or molecular biomarkers in BC.

Epigenetic disruption of histone deacetylase-2 accelerated apoptotic signaling and retarded malignancy in gastric cells.

Background: The objective of this research was to determine whether HDAC2 function is associated with gastric cancer progression. Methods: HDAC2 was knocked out in EPG85.257 cells using CRISPR/Cas9 and tumorigenesis pathways were evaluated. Results: Cell proliferation, colony formation, wound healing and transwell invasion were inhibited in ΔHDAC2:EPG85.257 cells. Quantitative analyses revealed a significant downregulation of MMP1, p53, Bax, MAPK1, MAPK3, pro-Caspase3, ERK1/2, p-ERK1/2, AKT1/2/3, p-AKT1/2/3, p-NF-κB (p65), Twist, Snail and p-FAK transcripts/proteins, while SIRT1, PTEN, p21 and Caspase3 were upregulated in ΔHDAC2:EPG85.257 cells. Conclusion: These results indicated that HDAC2 enhanced migration, colony formation and transmigration ability. HDAC2 inhibition may improve gastric cancer chemotherapy pathways.

DNA changes are the main causes of cancer. Therefore, finding easy ways to manipulate and correct DNA changes has been the biggest medical concern in cancer treatment. Researchers have introduced CRISPR/Cas9 as the newest technology for gene editing that precisely and easily changes the genome of any cell. In our study, histone deacetylase-2 was disrupted in gastric cancer cells using CRISPR technology. This modification reduced growth kinetics and invasion of cancer cells. On the other hand, cell death (also called apoptosis) was induced. Sensitization of the cancer cells to chemotherapeutic agents is noticeable in this research. This study needs to uncover more signaling pathways in vitro and in vivo.

MiR-548 K regulatory effect on the ABCG2 gene expression in MDR breast cancer cells.

BACKGROUND: multidrug resistance (MDR) is One of the foremost challenges in overcoming breast cancer. Various molecular processes are involved in the development of MDR in breast cancer cells, including over expression of ABC transporters such as ABCG2 (BCRP), increase breast cancer stem cells drug resistance, and epithelial mesenchymal transition. AIMS: In the present study, we used bioinformatics and experimental analysis to investigate the role of miR-548 K, in the modulating of ABCG2, in MDR breast cancer cells. METHODS AND RESULTS: In silico inspections introduce 14 microRNAs targeting 3'-UTR region of ABCG2 transcripts, which are probably involved in breast cancer drug resistance. An association was highlighted between miR-548 k with ABC transporter family. The expression level of ABCG2 gene in MCF7-MX cell lines was significantly more than MCF7 cell lines. On the other hand, we increased the expression of miR-548 K in MCF7-MX and MCF7 cell lines through its transfection, which dramatically coincided with decreasion in the ABCG2 transcripts level. Additional studies on patient samples revealed that the expression of ABCG2 showed an increase in ABCG2 level in neoadjuvant chemotherapy drugs resistance (NCDR) patients compared to primary pre-operative chemotherapy drugs response (PCDR) patients. Also, a reduction in the expression of miR-548 K in NCDR patients was revealed. CONCLUSION: The results of our study suggest that miR-548 K may be involved in modulating the expression of ABCG2 in MDR breast cancer cells.

Investigation of the therapeutic role of native plant compounds against colorectal cancer based on system biology and virtual screening.

This study investigated the anticancer effects of compounds extracted from native plants on colon cancer following drug-target-network analysis and molecular docking. Based on the ChEBI database, compounds were identified in medicinal plants and weeds in the Chaharmahal and Bakhtiari provinces of Iran. A drug-target network was constructed based on candidate colon cancer protein targets and selective compounds. Network pharmacology analysis was conducted against the identified compounds and subjected to molecular docking studies. Based on molecular dynamics simulations, the most efficient compounds were evaluated for their anticancer effects. Our study suggests that TREM1, MAPK1, MAPK8, CTSB, MIF, and DPP4 proteins may be targeted by compounds in medicinal plants for their anti-cancer effects. Multiorthoquinone, Liquiritin, Isoliquiritin, Hispaglabridin A, Gibberellin A98, Cyclomulberrin, Cyclomorusin A, and Cudraflavone B are effective anticancer compounds found in targeted medicinal plants and play an important role in the regulation of important pathways in colon cancer. Compounds that inhibit MIF, CTSB, and MAPK8-16 appear to be more effective. Additional in vitro and in vivo experiments will be helpful in validating and optimizing the findings of this study.

A comprehensive review of cancer therapies mediated by conjugated gold nanoparticles with nucleic acid.

Nucleic acids provide a promising therapeutic platform by targeting various cell signaling pathways involved in cancer and genetic disorders. However, maintaining optimal stability during delivery limits their utility. Nucleic acid delivery vehicles are generally categorized into biological and synthetic carriers. Regardless of the efficiency of biological vectors, such as viral vectors, issues related to their immunogenicity and carcinogenesis are very important and vital for clinical applications. On the other hand, synthetic vectors such as lipids or polymers, have been widely used for nucleic acid delivery. Despite their transfection efficiency, low storage stability, targeting inefficiency, and tracking limitations are among the limitations of the clinical application of these vectors. In the past decades, gold nanoparticles with unique properties have been shown to be highly efficient mineral vectors for overcoming these obstacles. In this review, we focus on gold nanoparticle-nucleic acid combinations and highlight their use in the treatment of various types of cancers. Furthermore, by stating the biological applications of these structures, we will discuss their clinical applications.

CRISPR/Cas9 as precision and high-throughput genetic engineering tools in gastrointestinal cancer research and therapy.

Gastrointestinal cancer (GI) is one of the most serious and health-threatening diseases worldwide. Many countries have encountered an escalating prevalence of shock. Therefore, there is a pressing need to clarify the molecular pathogenesis of these cancers. The use of high-throughput technologies that allow the precise and simultaneous investigation of thousands of genes, proteins, and metabolites is a critical step in disease diagnosis and cure. Recent innovations have provided easy and reliable methods for genome investigation, including TALENs, ZFNs, and the CRISPR/Cas9 (clustered regularly interspaced palindromic repeats system). Among these, CRISPR/Cas9 has been revolutionary tool in genetic research. Recent years were prosperous years for CRISPR by the discovery of novel Cas enzymes, the Nobel Prize, and the development of critical clinical trials. This technology utilizes comprehensive information on genes associated with tumor development, provides high-throughput libraries for tumor therapy by developing screening platforms, and generates rapid tools for cancer therapy. This review discusses the various applications of CRISPR/Cas9 in genome editing, with a particular focus on genome manipulation, including infection-related genes, RNAi targets, pooled library screening for identification of unknown driver mutations, and molecular targets for gastrointestinal cancer modeling. Finally, it provides an overview of CRISPR/Cas9 clinical trials, as well as the challenges associated with its use.

Herbal Medicines as Potential Inhibitors of SARS-CoV-2 Infection.

Coronavirus disease 2019 (COVID-19) is the result of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding molecular pathogenesis is an essential factor for the allocation of effective preventive measures and the development of targeted therapeutics against COVID-19. The genome of SARS-CoV-2 encodes structural and nonstructural proteins, which can be targets for compounds with potential therapeutic ability. On the other hand, the virus life cycle has stages susceptible to targeting by drug compounds. Many natural antiviral compounds have been studied and evaluated at the cellular and molecular levels with antiviral potential. Meanwhile, many studies over the past few months have shown that plant polysaccharides have a good ability to target proteins and stages of the virus life cycle. In this regard, in this review study, the virus specifications and infectious process and structural and functional components of SARSCoV- 2 will be reviewed, and then the latest studies on the effect of plant compounds with more focus on polysaccharides on viral targets and their inhibitory potential on the infectious process of COVID-19 will be discussed.

Beta-Secretase 1 (BACE1) Is Down-Regulated in Invasive Ductal Carcinoma of Breast.

BACKGROUND: The enzyme beta-secretase 1 (BACE1) and its antisense transcript (BACE1-AS) have been implicated in the pathogenesis of Alzheimer's disease. Moreover, several lines of evidence point to their contribution in tumorigenesis. METHODS: In the present study, we evaluated expression of BACE1 mRNA (BACE1) and BACE1-AS in 54 breast cancer tissues and 54 adjacent non-cancerous tissues (ANCTs) from the same patients using quantitative real-time PCR. RESULTS: BACE1 was significantly down-regulated in tumoral tissues compared with ANCTs, while BACE1- AS expression was not significantly different between tumoral tissues and ANCTs. The Bayesian Multilevel model showed a significant difference in BACE1 expression between stage 1 and 2 cancers after age-effect adjustments. BACE1-AS expression was significantly greater in ER-positive than in ER-negative samples (P=0.01). BACE1 and BACE1-AS expression were not correlated with patient ages in any sample sets. CONCLUSION: Significant correlations were detected between expression of these genes in both tumoral tissues and ANCTs. The current study provides evidence for differential BACE1 expression in breast tissues and suggests further assessment of the role of BACE1 in the pathogenesis of cancer.

A Survey on the Adjuvant Role of Naloxone Alone or Combined with Alum in Vaccination Against Fasciolosis in BALB/c Mice.

BACKGROUND: Fasciolosis is a zoonotic parasitic disease imposing a heavy load of livestock losses worldwide. PURPOSE: We aimed to evaluate immune-stimulatory effects of naloxone (NLX), an opioid receptor antagonist, in combination with alum in mice vaccinated with excretory-secretory antigens (E/S) of Fasciola hepatica. METHODS: 8-week-old female BALB/c mice were subcutaneously vaccinated using E/S antigens of F. hepatica. Experimental groups (14 mice per group) included: vaccine (E/S antigen), alum vaccine (E/S antigen plus alum), NLX vaccine (E/S antigen plus NLX), and alum-NLX vaccine (E/S antigen plus a mixture of alum-NLX). The control group was infused with PBS. Lymphocyte proliferation and the levels of IFN-γ, IL-4, IgG2a, IgG1, and total IgG were measured. RESULTS: Mice vaccinated with NLX or alum-NLX adjuvants showed significantly higher rates of lymphocyte proliferation, IFN-γ, total IgG, and IgG2a levels. The mice that were injected with alum showed a significantly higher concentration of IL-4. Ratios of IFN-γ/Il-4 and IgG2a/IgG1 were significantly higher in the NLX and alum-NLX groups in comparison with the groups vaccinated either with alum or without any adjuvant. A significantly higher protection rate (62.5%) was seen in mice vaccinated with the alum-NLX adjuvant compared to the other groups. CONCLUSION: NLX can be effective in conferring cellular immunity and protection against F. hepatica. It is recommended to consider this agent as a potential adjuvant in vaccines against fasciolosis.

Targeted cancer therapy through antibody fragments-decorated nanomedicines.

Active targeting in cancer nanomedicine, for improved delivery of agents and diagnose, has been reviewed as a successful way for facilitating active uptake of theranostic agents by the tumor cells. The application of a targeting moiety in the targeted carrier complexes can play an important role in differentiating between tumor and healthy tissues. The pharmaceutical carriers, as main part of complexes, can be polymeric nanoparticles, micelles, liposomes, nanogels and carbon nanotubes. The antibodies are among the natural ligands with highest affinity and specificity to target pharmaceutical nanoparticle conjugates. However, the limitations, such as size and long circulating half-lives, hinder reproducible manufacture in clinical studies. Therefore, novel approaches have moved towards minimizing and engineering conventional antibodies as fragments like scFv, Fab, nanobody, bispecific antibody, bifunctional antibody, diabody and minibody preserving their functional potential. Different formats of antibody fragments have been reviewed in this literature update, in terms of structure and function, as smart ligands in cancer diagnosis and therapy of tumor cells.

Apoptotic Effects of the B Subunit of Bacterial Cytolethal Distending Toxin on the A549 Lung Cancer Cell Line.

Cytolethal distending toxin (CDT) is a secreted tripartite genotoxin produced by many pathogenic gram-negative bacteria. It is composed of three subunits, CdtA, CdtB and CdtC, and CdtB-associated deoxyribonuclease (DNase) activity is essential for the CDT toxicity. In the present study, to design a novel potentially antitumor drug against lung cancer, the possible mechanisms of cdtB anticancer properties were explored in the A549 human lung adenocarcinoma cell line. A recombinant plasmid pcDNA3.1/cdtB was constructed expressing CdtB of human periodontal bacterium Aggregatibacter actinomycetemcomitans and investigated for toxic properties in A549 cells and possible mechanisms. It was observed that plasmid pcDNA3.1/cdtB caused loss of cell viability, morphologic changes and induction of apoptosis. Furthermore, measurement of caspase activity indicated involvement of an intrinsic pathway of cell apoptosis. Consequently, the recombinant plasmid pcDNA3.1/cdtB may have potential as a new class of therapeutic agent for gene therapy of lung cancer.

Recent advances on biocompatible and biodegradable nanoparticles as gene carriers.

INTRODUCTION: Gene therapy mainly depends on the use of appropriate delivery vehicles with no induction of immune responses and toxicity. The limitations of viral gene carriers such as induction of immunogenicity, random integration in the genome of the host, limitations in the size, has led to a movement toward non-viral systems with much safer properties. Biodegradable and biocompatible polymeric nanocarriers due to several unique properties such as excellent biocompatibility, prolonged gene circulation time, prevented gene degradation, passive targeting by using the enhanced permeability and retention (EPR) effect, and possibility of modulating polymers structure to obtain desirable therapeutic efficacy, are among the most promising systems for gene delivery. However, biodegradable gene delivery systems have some limitations such as inadequate stability and slow release of therapeutics which have to be overcome. Thus, a variety of advanced functional biodegradable delivery systems with more efficient gene delivery activity has recently been introduced. AREAS COVERED: This review summarizes different aspects of biodegradable and biocompatible nano carriers including formulation, mechanism of intracellular uptake, various potential applications of biodegradable nanoparticles and finally recent studies on the therapeutic efficacy of these nanoparticles in sustained delivery of genes. EXPERT OPINION: Biocompatible and biodegradable polymers will play a necessary and important role in developing new and safe carriers for oligonucleotide delivery. More working and the development of optimized polymers will reveal more their efficacy in the treatment of patients via helping in better gene therapy.

Modulation of the Immune Response to DNA Vaccine Encoding Gene of 8-kDa Subunit of Echinococcus granulosus Antigen B Using Murine Interleukin-12 Plasmid in BALB/c Mice.

BACKGROUND: The current study was designed to evaluate immune responses induced by DNA vaccines encoding 8-kDa subunit of antigen B (HydI) of Echinococcus granulosus and murine interleukin 12 (IL-12) as genetic adjuvants in BALB/c mice. METHODS: Expression plasmid pcDNA3.1 containing HydI (pcHyd1) as vaccine along with the murine interleukin 12 (pcMIL12) as adjuvant were used. Thirty-five mice in the five experimental groups received PBS, empty pcDNA3.1, pcHydІ, pcMIL-12, and pcHydІ+ pcMIL-12 in days zero, 14th and 28th. Two weeks after the last immunization, evaluation of the immune response was performed by evaluating the proliferation of splenic lymphocytes, IFN-γ and IL-4, determination of IgG isotyping titer. RESULTS: Mice that received the pcHydI+pcMIL12 exhibited higher levels of lymphocyte proliferation compared to mice that received the pcHydI alone (P<0.001), and produced significantly more IFN-γ in comparison to other groups (P< 0.001). In addition, they produced significantly less IL-4 than mice receiving the PBS and the empty plasmid (P<0.023). The IgG2a levels were clearly higher in pcHydI+pcMIL12 group in comparison with the groups of pcHydI alone, empty plasmid, and PBS. In contrast, IgG1 was elevated in the group of pcHydI. CONCLUSION: Co-delivery of IL-12 with DNA encoding 8-kDa subunit of antigen B was effective significantly in inducing the immune response in mice.