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Background There is a demand for easy, rapid and affordable analysis of biological contaminants in foods to guarantee their safety and quality. Most analysis of food contaminants is commonly performed in a limited number of samples in centralized laboratories by an expert technician. Therefore, developing of alternative techniques such as portable biosensors is of great significance. Scope and approach This review aims to discuss the recent advances in designing and applying of portable biosensors for the detection of biological food contaminants including bacteria, fungi and the related toxins. Also, the review deals briefly the basic knowledge of various portable biosensors which have been developed for the contaminants detection. Moreover, the developed portable biosensors for different biological contaminants are discussed in details. Key findings and conclusions Portable biosensors are tiny, accessible and movable diagnostic devices which provide online detection of biological contaminations. Nanotechnology, microfluidic, electronic and biological design strategies as well as wireless networking capabilities help researchers to design and developed portable biosensors. During the recent years several portable devices with high sensitivity and selectivity have been developed for the monitoring biological food contaminants. These biosensors are based on various principles, such as electrochemical, magnetic and optical properties. Introduction of recent advances of the portable biosensors will help researchers to design or promote novel and advanced portable biosensors for food contaminants detection.

Background Colorectal cancer which is related to genetic and environmental risk factors, is among the most prevalent life-threatening cancers. Although several pathogenic bacteria are associated with colorectal cancer etiology, some others are considered as highly selective therapeutic agents in colorectal cancer. Nowadays, researchers are concentrating on bacteriotherapy as a novel effective therapeutic method with fewer or no side effects to pay the way of cancer therapy. The introduction of advanced and successful strategies in bacterial colorectal cancer therapy could be useful to identify new promising treatment strategies for colorectal cancer patients. Main text In this article, we scrutinized the beneficial effects of bacterial therapy in colorectal cancer amelioration focusing on different strategies to use a complete bacterial cell or bacterial-related biotherapeutics including toxins, bacteriocins, and other bacterial peptides and proteins. In addition, the utilization of bacteria as carriers for gene delivery or other known active ingredients in colorectal cancer therapy are reviewed and ultimately, the molecular mechanisms targeted by the bacterial treatment in the colorectal cancer tumors are detailed. Conclusions Application of the bacterial instrument in cancer treatment is on its way through becoming a promising method of colorectal cancer targeted therapy with numerous successful studies and may someday be a practical strategy for cancer treatment, particularly colorectal cancer.

Colorectal cancer (CRC) is a universal heterogeneous disease that is characterized by genetic and epigenetic alterations. Immunotherapy using monoclonal antibodies (mAb) and cancer vaccines are substitute strategies for CRC treatment. When cancer immunotherapy is combined with chemotherapy, surgery, and radiotherapy, the CRC treatment would become excessively efficient. One of the compelling immunotherapy approaches to increase the efficiency of CRC therapy is the deployment of therapeutic mAbs, nanobodies, bi-specific antibodies and cancer vaccines, which improve clinical outcomes in patients. Also, among the possible therapeutic approaches for CRC patients, gene vaccines in combination with antibodies are recently introduced as a new perspective. Here, we aimed to present the current progress in CRC immunotherapy, especially using Bi-specific antibodies and dendritic cells mRNA vaccines. For this aim, all data were extracted from Google Scholar, PubMed, Scopus, and Elsevier, using keywords cancer vaccines; CRC immunotherapy and CRC mRNA vaccines. About 97 articles were selected and investigated completely based on the latest developments and novelties on bi-specific antibodies, mRNA vaccines, nanobodies, and MGD007.

Stem cells are considered to have significant capacity to differentiate into various cell types in humans and animals. Unlike specialized cells, these cells can proliferate several times to produce millions of cells. Nowadays, pluripotent stem cells are important candidates to provide a renewable source for the replacement of cells in tissues of interest. The damage to neurons and glial cells in the brain or spinal cord is present in neurological disorders such as Amyotrophic lateral sclerosis, stroke, Parkinson’s disease, multiple sclerosis, Alzheimer’s disease, Huntington’s disease, spinal cord injury, lysosomal storage disorder, epilepsy, and glioblastoma. Therefore, stem cell transplantation can be used as a novel therapeutic approach in cases of brain and spinal cord damage. Recently, researchers have generated neuron-like cells and glial-like cells from embryonic stem cells, mesenchymal stem cells, and neural stem cells. In addition, several experimental studies have been performed for developing stem cell transplantation in brain tissue. Herein, we focus on stem cell therapy to regenerate injured tissue resulting from neurological diseases and then discuss possible differentiation pathways of stem cells to the renewal of neurons.

Long non-coding RNAs (lncRNA) have been emerged as a novel class of molecular regulators in cancer. They are dysregulated in many types of cancer; however, there is not enough knowledge available on their expression and functional profiles. Lung cancer is the leading cause of the cancer deaths worldwide. Generally, lncRNAs may be associated with lung tumor pathogenesis and they may act as biomarkers for the cancer prognosis and diagnosis. Compared to other invasive prognostic and diagnostic methods, detection of lncRNAs might be a user-friendly and noninvasive method. In this review article, we selected 27 tumor-associated lncRNAs by literature reviewing to further discussing in detail for using as diagnostic and prognostic biomarkers in lung cancer. Also, in an in silico target analysis, the "Experimentally supported functional regulation" approach of the LncTarD web tool was used to identifying the target genes and regulatory mechanisms of the selected lncRNAs. The reports on diagnostic and prognostic potential of all selected lncRNAs were discussed. However, the target genes and regulatory mechanisms of the 22 lncRNAs were identified by in silico analysis and we found the pathways that are controlled by each target group of lncRNAs. They use epigenetic mechanisms, ceRNA mechanisms, protein interaction and sponge mechanism. Also, 10, 23, 5, and 28 target genes for each of these mechanisms were identified, respectively. Finally, each group of target genes controls 50, 12, 7, and 2 molecular pathways, respectively. In conclusion, LncRNAs could be used as biomarkers in lung cancer due to their roles in control of several signaling pathways related to lung tumors. Also, it seems that lncRNAs, which use epigenetic mechanisms for modulating a large number of pathways, could be considered as important subjects for lung cancer-related diagnostic and prognostic biomarkers.

Background Quinolones are broad-spectrum antibiotics, which are used for the treatment of different infectious diseases associated with Enterobacteriaceae. During recent decades, the wide use as well as overuse of quinolones against diverse infections has led to the emergence of quinolone-resistant bacterial strains. Herein, we present the development of quinolone antibiotics, their function and also the different quinolone resistance mechanisms in Enterobacteriaceae by reviewing recent literature. Methods All data were extracted from Google Scholar search engine and PubMed site, using keywords; quinolone resistance, Enterobacteriaceae, plasmid-mediated quinolone resistance, etc. Results and conclusion The acquisition of resistance to quinolones is a complex and multifactorial process. The main resistance mechanisms consist of one or a combination of target-site gene mutations altering the drug-binding affinity of target enzymes. Other mechanisms of quinolone resistance are overexpression of AcrAB-tolC multidrug-resistant efflux pumps and downexpression of porins as well as plasmid-encoded resistance proteins including Qnr protection proteins, aminoglycoside acetyltransferase (AAC(6′)-Ib-cr) and plasmid-encoded active efflux pumps such as OqxAB and QepA. The elucidation of resistance mechanisms will help researchers to explore new drugs against the resistant strains.

Background: Aquatic microorganisms have an important role in the bioremediation of environmental pollutants. Polycyclic Aromatic Hydrocarbons (PAHs) are described as dangerous pollutants that can bind covalently to the nucleic acids, causing mutations. Therefore, they have carcinogenic and toxic properties. Also, are involved in diseases such as asthma, lung dysfunction, and chronic bronchitis. This study aimed to isolate and characterize aquatic bio-degrading bacteria from the world’s largest lake, Khazar, with the ability to use PAHs as only carbon source. Methods: Samples were taken from the estuary of Siah Rud River (Mazandaran province, Iran) and Fereydunkenar beach leading to isolation of twenty-three bacteria on marine agar and sea water media. The isolates were cultured on separate ONR7a medium, each supplemented with only one PAH; as the sole carbon source; including naphthalene, phenanthrene, and anthracene. Results: Eleven bacterial isolates were able to grow on supplemented media: TBZ-E1, TBZ-E2, TBZ-E3, TBZ-S12, TBZ-S16, TBZ-E20, TBZ-SF2, TBZ-F1, TBZ-F2, TBZ-F3 and TBZ2. These isolates belong to Alteromonas, Marivivens, Pseudoalteromonas, Vibrio, Shewanella, Photobacterium, Mycobacterium and Pseudomonas genera. The qualitative analysis showed that the consortium of isolates TBZ-F1, TBZ-F2, TBZ-F3, TBZ-SF2, and TBZ2 displayed the highest degradation rate for phenanthrene and naphthalene. Naphthalene, phenanthrene, and anthracene were potently degraded by TBZ2 and TBZ-SF2 and accordingly were subjected to measure degradation potential of mentioned PAHs. Conclusion: The bacterial isolates of Caspian lake have a critical duty in biodegradation of PAHs. These isolates are representative samples of the bacterial population of this lake, participating in the purification process of this habitat.

Background : Recently, resistant pathogenic microorganisms have become increasingly wide spread. The search for new natural antibiotics is a viable solution to this problem. For this aim we investigated the antimicrobial ability of Tabrizicola aquatica, the novel bacterium isolated from Qurugol Lake located nearby Tabriz city, Iran. Methods: The antimicrobial properties of Tabrizacola aquatica was investigated using well diffusion test. Tabtizicola aquatica was incubated at 40℃ in shaking incubator at 150 rpm for 14 days. The culture was centrifuged to obtain cell free supernatant, which was sterilized using 0.2 μm filter paper and lyophilized. Microorganisms were lawn and then wells were prepared over the agar plates. About 100 ml of the diluted lyophilized supernatant was added to the wells. The plates then were incubated at 37℃. After 48 hours, antimicrobial activity was defined by measuring the inhibition zone diameter. Results: The bacterial filtrates had considerable antagonistic effect against Escherichia coli, Rhizobium radiobacter, Pseudomonas syringae, Erwinia amylovora, Botrytis cinerea, Neurospora crassa and Fusarium oxysporum. However, the filtrates did not show any inhibitory action on the Aspergillus flavus and Klebsiella pneumonia. The supernatant decreased the growth zone on Streptococcus aureus, Pseudomonas aeruginosa, Shigella flexneri, Xanthomonas camoestris and Bassilus cereos. The result of MIC against pathogens was found for Neurospora crassa in the 50 µg/mL. Conclusion: The results, suggested that Tabrizicola aquatica and similar bacteria can be helpful to control freshwater natural water sources from pathogenic microorganism. Moreover, microbial natural products are still the most promising source of new antibiotics. Our results point out a scope for characterization of the metabolites and could be a candidate in the identification of novel antibiotics.

Helicobacter pylori (H. pylori) infection is considered as one of the main cause of gastric cancer. Treatment failure of the infection often occurs due to antibiotic resistance. Herein, we aimed to evaluate the mutations in 23S rRNA gene of H. pylori which are associated with clarithromycin resistance and in rdxA and frxA genes of the bacterium which may be associated with metronidazole resistance, in paraffin-embedded gastric biopsies from patients with gastric adenocarcinoma and gastritis in Tabriz, the northwest of Iran. In the study, 80 paraffin-embedded tissue sections from 40 gastric cancer and 40 gastritis patients in the Imam Reza hospital, Tabriz, Iran were collected. The existence of ureC gene was verified by PCR method. Genotypical clarithromycin resistance was investigated by real-time PCR method and determination of the melting temperature. PCR reaction and sequencing were used for the evaluation of mutations in rdxA and frxA genes. The results of ureC amplification showed that DNA of H. pylori was present in the 82.66% of the obtained DNA samples. About 45.16% of samples were resistant to the clarithromycin and 53.22% of them were resistant to the metronidazole. Based on the results from real-time PCR, the frequency of mutations was as follow A2143G 64.28%, A2142G 44.44% and A2142C 1.11%. The mutations of rdxA gene were 66.66% missense, 30.30% frameshift and 3.03% non-sense. The mutations of frxA gene were 36.36% missense, 54.54% frameshift and non-sense 9.09%. A2143G mutation is the most frequent mutation among clarithromycin resistant genes in Iran. Also, missense and frameshift mutations are frequent in rdxA and frxA genes. Screening for these mutations could help researchers to investigate the most effective anti-H. pylori antibiotics and to prevent antibiotic resistance.

Breast cancer is a major clinical challenge that affects a wide range of the female population and heavily burdens the health system. In the past few decades, attempts have been made to understand the etiology of breast cancer, possible environmental risk factors, and the genetic predispositions, pathogenesis, and molecular aberrations involved in the process. Studies have shown that breast cancer is a heterogeneous entity; each subtype has its specific set of aberrations in different cell signaling pathways, such as Notch, Wnt/β-catenin, transforming growth factor-β, and mitogen-activated protein kinase pathways. One novel group of molecules that have been shown to be inducted in the regulation of multiple cell signaling pathways is the long noncoding RNAs (lncRNAs). These molecules have important implications in the regulation of multiple signaling pathways by interacting with various genes, affecting the transcription process, and finally, playing roles in posttranslational control of these genes. There is growing evidence that lncRNAs are involved in the process of breast cancer formation by effecting the aforementioned signaling pathways, and that this involvement can have significant diagnostic and prognostic values in clinical contexts. The present review aims to elicit the significance of lncRNAs in the regulation of cell signaling pathways, and the resulting changes in cell survival, proliferation, and invasion, which are the hallmarks of breast cancer.

Colorectal cancer (CRC) is one of the most lethal and prevalent cancers throughout the world. Despite the remarkable advance in the field, drug resistance still remains as an unresolved problem in cancer. Hence, finding effective compounds with minimal side effects to fight cancer is of central priority. Herbal products have been traditionally used to prevent and treat a variety of diseases. In the present study, the antitumor effect of Terminalia catappa plant ethanolic extract (TCE) was assessed on SW480 CRC model cell line. In this regard, effects of TCE were evaluated on the proliferation, apoptosis, and migration of SW480 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Annexin V/PI flow cytometry, and scratch tests, respectively. Furthermore, changes in the expression of genes involved in these events including Bax, Bcl-2, Caspase 3, Caspase 8, Caspase 9, MMP-13, miR-21, and miR-34a were measured by quantitative real-time PCR (qRT-PCR). According to the MTT results, TCE reduced the proliferation of SW480 cells significantly. The flow cytometry test also revealed a notable rate of apoptosis induction after TCE treatment. An inhibitory effect on cell migration was also evident in scratch test. Expression patterns of the assessed genes also changed subsequent to TCE treatment. The results of this study indicated that T. catappa could be considered as a potential source of anticancer compounds and a candidate for further investigations.

Breast cancer is one of the most lethal malignancies in women in the world. Various factors are involved in the development and promotion of the malignancy; most of them involve changes in the expression of certain genes, such as microRNAs (miRNAs). MiRNAs can regulate signaling pathways negatively or positively, thereby affecting tumorigenesis and various aspects of cancer progression, particularly breast cancer. Besides, accumulating data demonstrated that miRNAs are a novel tool for prognosis and diagnosis of breast cancer patients. Herein, we will review the roles of these RNA molecules in several important signaling pathways, such as transforming growth factor, Wnt, Notch, nuclear factor-κ B, phosphoinositide-3-kinase/Akt, and extracellular-signal-regulated kinase/mitogen activated protein kinase signaling pathways in breast cancer.

Antimicrobial peptides (AMPs) are a crucial part of innate immunity that exist in the most of living organisms. In fact, AMPs have ability to incite the innate immune response and combat with a broad range of microbes, including bacteria, virus, parasite and fungi. Moreover, recent studies indicated that, the small cationic peptides have ability to target cancer cells and can be used as the cancer therapeutic agents. AMPs are the very tiny macromolecules, commonly in the range of 6 to 100 amino acids. During last decades with the growing antibiotic resistance, AMPs have gained considerable attention because of potential application to combat multidrug-resistant microorganisms. Therefore, herein we aimed to review the features of antibacterial peptides, including their classification, structure, source, mechanism of action and clinical application. Furthermore, problems in the production of recombinant peptides and also newest researches in the clinical developments of AMPs for treatment of crucial diseases; particularly cancers will be reviewed.

Gastric cancer is an aggressive disease which is the fourth prevalent malignancy in the world. Beside the genetic factors, epigenetic alterations such as promoter CpG island hyper methylation are involved in the emergence of gastric cancer. Herein, we investigated the methylation status of CDH11, EphA5, and HS3ST2 genes in patients with and without gastric adenocarcinoma for the first time. In the study 40 paraffin-embedded tissue sections from gastric adenocarcinoma patients and 40 specimens from patients with functional dyspepsia were taken. DNA extraction was performed using a modified salting out method. Epizen DNA methylation kit was used to the bisulfite DNA conversion. The methylation status of CDH11, EphA5, and HS3ST2 genes were analyzed by methylation-specific PCR (MSP) technique. Among the 80 specimens, 71 DNA samples were achieved (34 gastric adenocarcinoma patients and 37 control patients). The results showed that CDH11, EphA5, and HS3ST2 genes are methylated in 28 (82.45%), 19 (55.88%), and 26 (76.47%) of 34 DNA samples from gastric adenocarcinoma patients, respectively, whereas, these genes are methylated in 7 (18.91%), 9 (24.32%) and 7 (18.91%) of 37 samples from noncancerous patients, respectively. Statistical analyses using a chi-squared test showed that there is a statistically significant difference in methylation level of CDH11, EphA5, and HS3ST2 genes between gastric cancer and uncancerous patients (p

Coronary artery disease (CAD) is primarily caused by atherosclerosis, which is a series of chronic inflammatory processes leading to the initiation and progression of vascular endothelial cell injury enhancing plaque formation. As critical components of the immune system, peripheral blood mononuclear cells (PBMCs) actively cross-talk with pathophysiological conditions induced by endothelial cell injury, reflecting in altered PBMC expression pattern. This study explored PBMC expression levels of miR-21, miR-25 and PTEN in patients with angiographically proven significant coronary stenosis (the CAD group), patients with insignificant coronary stenosis (the ICAD group) and healthy subjects, and assessed potentials of PBMC expressions in discriminating groups of study subjects. In-silico analysis was also performed to obtain insights into CAD-related pathways and biological processes that may be influenced by altered miRNA expressions. A reduced level of PBMC miR-21 was observed in the ICAD group compared to the CAD group (P: 0.004) or healthy controls (P: 0.0001). PBMC miR-21 level was negatively correlated with the PTEN expression (Spearman r: -0.43, P: 3.9e-09). The PTEN expression was increased in the CAD or ICAD group compared to the control group (CAD vs. controls P: 0.0003, ICAD vs. controls P: 0.03). A stepwise increase in PBMC miR-25 levels was observed from healthy controls to ICADs and CAD patients (Kruskal-Wallis P: 7.68e-12). PBMC gene expressions had reasonable power to discriminate between pairs of study groups. PBMC miR-21 levels were able to discriminate ICADs from both CADs and controls and miR-25 levels had potentials to differentiate among all pairs of study groups (i.e. CADs-ICADs, CADs-controls, CADs-all other subjects, ICADs-controls). PBMC PTEN expression was able to discriminate patients with CAD or ICAD from control subjects. Overrepresentation enrichment analysis of experimentally validated targets of miR-21 and miR-25 highlighted key biological processes and pathways, such as "angiogenesis" and "leukocyte cell-cell adhesion", that may be influenced by dysregulation of PBMC miR-21 and miR-25. In conclusion, these findings suggest that patients with insignificant coronary stenosis may have a distinct PBMC miRNA expression profile than those with significant stenosis or healthy controls.

Codelivery is a promising strategy of targeted delivery of cytotoxic drugs for eradicating tumor cells. This rapidly growing method of drug delivery uses a conjugate containing drug linked to a smart carrier. Both two parts usually have therapeutic properties on the tumor cells. Monoclonal antibodies and their derivatives, such as Fab, scFv, and bsAb due to targeting high potent have now been attractive candidates as drug targeting carrier systems. The success of some therapeutic agents like small interfering RNA (siRNA), a small noncoding RNAs, with having problems such as enzymatic degradation and rapid renal filtration need to an appropriate carrier. Therefore, the aim of this study is to review the recent enhancements in development of antibody drug conjugates (ADCs), especially antibody-siRNA conjugates (SRCs), its characterizations and mechanisms in innovative cancer therapy approaches.

MicroRNAs (miRNAs) have emerged as a critical component of regulatory networks that modulate and fine-tune gene expression in a post-transcriptional manner. The microRNA-196 family is encoded by three loci in the human genome, namely hsa-mir-196a-1, hsa-mir-196a-2, and hsa-mir-196b. Increasing evidence supports the roles of different components of this miRNA family in regulating key cellular processes during differentiation and development, ranging from inflammation and differentiation of stem cells to limb development and remodeling and structure of adipose tissue. This review first discusses about the genomic context and regulation of this miRNA family and then take a bird's eye view on the updated list of its target genes and their biological processes to obtain insights about various functions played by members of the microRNA-196 family. We then describe evidence supporting the involvement of the human microRNA-196 family in regulating critical cellular processes both in physiological and non-malignant inflammatory conditions, highlighting recent seminal findings that carry implications for developing novel therapeutic or diagnostic strategies.

Background: magnetic nanocomposites with a core-shell nanostructure has huge applications in different sciences especially in the release of the drugs, because of their exclusive physical and chemical properties. In this research, magnetic@layered double hydroxide multicore@shell nanostructure was synthesized by the facile experimentand is used as novel drug nanocarrier.Methods: Magnetic nanospheres were synthesized by a facile one-step solvothermal route, and in following, layered double hydroxide nanoflakes were prepared on the magnetic nanospheres by coprecipitation experiment. The synthesized nanostructures were characterized by FTIR, XRD, SEM, VSM and TEM, respectively. After intercalation with Ibuprofen and Diclofenac as the anti-inflammatory drugs by using exchange anion experiment, the basal spacing of synthesized layered double hydroxides were compared with brucite nanosheets from 0.48 nm to 2.62 nm and 2.22 nm, respectively. Results: The results indicated Ibuprofen and Diclofenac were successfully intercalated into the interlay space of LDHs by bridging bidentate interaction. Besides, in vitro drug release experiments in pH 7.4, Phosphate-buffered saline (abbreviated PBS) showed the constant release profiles with Ibuprofen and diclofenac as model drugs with different lipophilicity and water solubility and size and steric effect. Conclusions: The Fe3O4@LDH-ibuprofen and Fe3O4@LDH-diclofenac had the advantage of the strong interaction between the carboxyl groups with higher trivalent cations by bridging bidentate, clarity and high thermal stability. We confirm, which Fe3O4@LDH multicore-shell nanostructure will have potential application for constant drug delivery.

Breast cancer is a heterogeneous malignancy and is the second leading cause of mortality among women around the world. Increasing the resistance to anti-cancer drugs in breast cancer cells persuades researchers to search the novel therapeutic approaches for the treatment of this malignancy. Among the novel methods, therapeutic peptides that target and disrupt tumor cells have been of great interest. Therapeutic peptides are short amino acid monomer chains with high specificity to bind and modulate a protein interaction of interest. Several advantages of peptides, such as specific binding on tumor cells surface, low molecular weight, and low toxicity on normal cells, make the peptides appealing therapeutic agents against solid tumors, particularly breast cancer. Also, the National Institutes of Health (NIH) describes therapeutic peptides as a suitable candidate for the treatment of drug-resistant breast cancer. In this review, we attempt to review the different therapeutic peptides against breast cancer cells that can be used in the treatment and diagnosis of the malignancy. Meanwhile, we presented an overview of peptide vaccines that have been developed for the treatment of breast cancer.

Colorectal cancer (CRC) is the fourth most common cause of cancer and mortality worldwide and is the third most common cancer in men and women. Surgery, radiotherapy, and chemotherapy are conventionally used for the treatment of colorectal cancer. However, these methods are associated with various side effects on normal cells. Thus, new studies are moving towards more effective and non-invasive methods for treatment of colorectal cancer. Targeted therapy of CRC is a promising new approach to enhance the efficiency and decrease the toxicity of the treatment. In targeted therapy of CRC, antibody fragments can directly inhibit tumor cell growth and proliferation. They also can act as an ideal carrier for targeted delivery of anticancer drugs. In the present study, the structure and function of different formats of antibody fragments, immune-targeted therapy of CRC using antibody fragments will be discussed.

Melanoma is the most serious type of skin cancer which develops from the occurrence of genetic mutations in the melanocytes. Based on the features of melanoma tumors such as location, genetic profile and stage, there are several therapeutic strategies including surgery, chemotherapy, and radiotherapy. However, because of the appearance resistance mechanisms, the efficiency of these treatments strategies may be reduced. It has been demonstrated that therapeutic monoclonal antibodies can improve the efficiency of melanoma therapies. Recently, several mAbs, such as nivolumab, pembrolizumab, and ipilimumab, were approved for the immunotherapy of melanoma. The antibodies inhibit immune checkpoint receptors such as CTL4 and pd-1. Another therapeutic strategy for the treatment of melanoma is cancer vaccines, which improve clinical outcomes in patients. The combination therapy using antibodies and gene vaccine give us a new perspective in the treatment of melanoma patients. Herein, we present the recent progressions in the melanoma immunotherapy, especially dendritic cells mRNA vaccines by reviewing recent literature.

Abstract: Muscle-specific miRNAs, which are known as MyomiRs, are crucial regulatory elements for cardiovascular development. MyomiRs are abundantly expressed in the myocardium and regulate certain aspects of physiological and pathological processes in myocardiocytes, including cardiovascular development, myocardial remodeling, and arise for cardiovascular diseases through different mechanisms, such as epigenetic pathways. Clinical and experimental studies have confirmed the myomiRs as promising diagnostic biomarkers for the early diagnosis of cardiac disorders. In this review, we have summarized recent findings in the field of epigenetic modulations of myomiRs and cardiac regeneration associated with cardiac diseases.

Ovarian cancer is one of the most lethal gynecologic cancers. The high mortality rate is due to lack of early symptoms and developing drug resistance. Immunotherapy has emerged as a promising approach to treatment of cancer. Bevacizumab is a recombinant humanized monoclonal IgG antibody against VEGF A that used in cancer immunotherapy, especially in ovarian cancer therapy. For a successful cancer immunotherapy the different features of therapeutic antibodies such as binding affinity should be improved. Increased affinity enhances the biological action of the antibody, which in turn improves the therapeutic effects. Furthermore, the increased antibody affinity can reduce the therapeutic dose of the antibody, resulting in lower toxicity and handling cost. Considering the importance of this issue, using in silico analysis, we aimed to find the important amino acids of the Bevacizumab antibody, and then replaced these amino acids with others to improve antibody binding affinity. Finally, we examined the binding affinity of antibody variants to antigens. In conclusion, the designed antibodies could be potential candidates for binding to antigens with improved affinity.

Ovarian cancer (OC) is the fifth leading cause of cancer-related death among women. The high mortality rate is due to lack of early symptoms, late diagnosis, limited treatment options, and also emerging of drug resistance. Todays, molecular markers have become promising in tumor-targeted therapy. Several molecular markers have been known in OC immunotherapy. Identification of the specific molecular markers with prognostic significance is interested. CD24 is a small sialoglycoprotein which is localized in lipid rafts through its glycosylphosphatidylinositol (GPI) anchor. It has been reported that CD24 is overexpressed in many cancers including OC. Also, CD24 is identified as a cancer stem cell marker in OC. The CD24 expression is associated with the development, invasion, and metastasis of cancer cells. The exact role of CD24 in cancer cells is not clearly understood. Recently, CD24 has been identified as an independent prognostic marker of survival in patients with OC. In this study, we reviewed the molecular targets in OC immune-targeted therapy and also presented an overview of the new molecular marker CD24 and its association with the OC by reviewing the recent literature.

Colorectal cancer (CRC) is the third most frequent cancer in human beings and is also the major cause of death among the other gastrointestinal cancers. The exact mechanisms of CRC development in most patients remains unclear. So far, several genetically, environmental and epigenetically risk factors have been identified for CRC development. The circadian rhythm is a 24-h rhythm that drives several biologic processes. The circadian system is guided by a central pacemaker which is located in the suprachiasmatic nucleus (SCN) in the hypothalamus. Circadian rhythm is regulated by circadian clock genes, cytokines and hormones like melatonin. Disruptions in biological rhythms are known to be strongly associated with several diseases, including cancer. The role of the different circadian genes has been verified in various cancers, however, the pathways of different circadian genes in the pathogenesis of CRC are less investigated. Identification of the details of the pathways in CRC helps researchers to explore new therapies for the malignancy.

The quality analysis of water, pharmaceutical and environmental compounds is a basic subject for human health. The presence of low-quality drugs, biological toxins and chemical compounds in water or forbidden additives in the nourishments lead to irreversible problems in human health. Hence, multiple analytical approaches have been presented for investigating the quality of environmental, pharmaceutical, and food compounds and monitoring the detection of toxic compounds and pollutants in water. Sensing tools based on analytical strategies are required for identifying and quantifying the different pollutants including biological and chemical contaminants in water samples. Among different biosensing and sensing tools, portable sensing assays are of special importance because of their great advantages such as simplicity, affordability, portability and ability to on-site detection. Therefore, during the last decades, designing and fabricating portable assays with great sensitivity and selectivity have been considered by many researchers and scientists for detection of various water pollutants. In this paper, the latest improvements in portable biosensors and sensors in the monitoring of biological and chemical pollutants in different samples of water are extensively explained. Initially, different portable sensing assays and novel technologies in their development are addressed. Then, by introducing various biological (bacteria, algae, toxins) and chemical pollutants (heavy metals, aromatic compounds, pesticides and insecticides), different portable sensors which have been developed for the detection of the pollutants are presented. Finally, upcoming perspectives and future challenges are thoroughly described.

Psychrotrophs or psychrophiles are extremophilic microorganisms that have the maximum temperature above 20 °C for growth. Since around 70% of the earth's biosphere temperature is below 5 °C, psychrotrophs could be found in diversity of species. These bacteria are source of enzymes, mainly including proteases used in different food industries where main reactions should be proceeded in low temperatures to save the aroma and flavor of food materials and bioactivity of valuable food ingredients such as bioactive peptides. Proteases are among the major groups of industrial enzymes accounting for 60% of the total global trade of enzymes. In this review, at first, we describe the biology, classification and physiological functions of different proteases obtained from psychrotrophic bacteria. Then, we present the various methods to produce and purify these enzymes from the bacteria. Moreover, we discuss several applications of the proteases to produce bioactive peptides from versatile protein sources. A comprehensive introduction to different types of proteases and their production and purification methods could help researchers identify novel proteases with improved properties, considering that their total market is significantly growing every year.

Colorectal cancer (CRC) is one of the most lethal and prevalent cancers throughout the world. Despite the remarkable advance in the field, drug resistance still remains as an unresolved problem in cancer. Hence, finding effective compounds with minimal side effects to fight cancer is of central priority. Herbal products have been traditionally used to prevent and treat a variety of diseases.In the present study, the antitumor effect of Terminalia catappa plant ethanolic extract (TCE) was assessed on SW480 CRC model cell line. In this regard, effects of TCE were evaluated on the proliferation, apoptosis, and migration of SW480 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Annexin V/PI flow cytometry, and scratch tests, respectively. Furthermore, changes in the expression of genes involved in these events including Bax, Bcl-2, Caspase 3, Caspase 8, Caspase 9, MMP-13, miR-21, and miR-34a were measured by quantitative real-time PCR (qRT-PCR).According to the MTT results, TCE reduced the proliferation of SW480 cells significantly. The flow cytometry test also revealed a notable rate of apoptosis induction after TCE treatment. An inhibitory effect on cell migration was also evident in scratch test. Expression patterns of the assessed genes also changed subsequent to TCE treatment.The results of this study indicated that T. catappa could be considered as a potential source of anticancer compounds and a candidate for further investigations.

Micro ribose nucleic acid (miRNA) recognition is of remarkable significance in the investigation of its functions as well as diagnosis of various diseases. The significance of miRNA itself is owing to the complex regulatory roles in several physiological processes and its close association with important diseases such as cardiovascular problems, diabetes, Alzheimer's disease and different kinds of cancers. On the other hand, there are numerous challenges to conquer in the recognition of miRNA, consisting of low abundance, varied concentration range, small size, prolonged extraction process from cells and sequence resemblances. Traditional approaches for miRNA recognition do not meet the present demands; therefore, several fast and effective strategies have been developed with a superior focus on specificity and sensitivity such as molecular beacon (MB) probes. These probes have been widely used for miRNA monitoring with high sensitivity both in living cells and in vitro. Compared to other systems, such as qRT-PCR, studies demonstrated that MB probes can be applied as effective equipment for assaying miRNAs by taking their advantages e.g. good specificity, short hybridization period, and easy operation. Therefore, this review highlights astonishing abilities and structure of MBs and their principle. Also, the use of atomic thickness nanomaterials such as quantum dots, molybdenum disulfide, and molybdenum carbide are introduced. Moreover, new advances in developing MB approaches that are able to trace miRNA in living cells and in vivo are discussed.

Gastric cancer is a complex heterogeneous disease which is the fourth prevalent malignancy worldwide. Although, several diagnosis and treatment are available for the gastric cancer patients, however the malignancy is still the third leading cause of cancer-related death in the world. Beside the genetic and environmental factors, epigenetic alterations are also involved in the emergence of gastric cancer. Epigenetics alterations are heritable changes which regulate gene expression without occurring changes in DNA sequence. Epigenetic changes mostly include DNA methylation, histon post-translational modifications, chromatin remodeling and non-coding RNAs. Among the mentioned epigenetic modifications, DNA methylation is a major epigenetic process that plays a key role in different stages of evolution and cancer development. In this review, we address all types of related epigenetic modifications in gastric cancer by focus on DNA methylation by reviewing the recent literatures. Understanding of molecular mechanisms of epigenetics alterations in gastric cancer development helps researchers to identify new epigenetic drugs against the malignancy.

Initiation of cancer is interconnected with different factors like infections. It has been estimated that infections, particularly viruses, participate in about 20% of all cancers. Bacteria as the most common infectious agents are also reported to be emerging players in the establishment of malignant cells. Microbial infections are able to modulate host cell transformation for promoting malignant features through the production of carcinogenic metabolites participating in inflammation responses, disruption of cell metabolism, and integrity and also genomic or epigenetic manipulations. It seems that the best example of the role of bacteria in cancer promotion is Helicobacter pylori infection, which is related to gastric cancer. World Health Organization (WHO) describes bacterium as class I carcinogens. Several bacterial infections have been reported in association with prevalent cancers. In this review, we will summarize the role of known bacterial infections in the initiation of the main common cancers, which show high mortality in the world. Examining the microbiomes in cancer patients is important and necessary to better understand the pathogenesis of this disease and also to plan therapeutic interventions.

Cyclin Dependent Kinase 9 (CDK9) as a serine/threonine kinase belongs to a great number of CDKs. CDK9 is the main core of PTEF-b complex and phosphorylates RNA polymerase (RNAP) II besides other transcription factors which regulate gene transcription elongation in numerous physiological processes. Multi-functional nature of CDK9 in diverse cellular pathways proposes that it is as an appealing target. In this review, we summarized the recent findings on the molecular interaction of CDK9 with critical participant molecules to modulate their activity in various diseases. Furthermore, the presented review provides a rationale supporting the use of CDK9 as a therapeutic target in clinical developments for crucial diseases; particularly cancers will be reviewed.

Background: MicroRNAs (miRNAs) play an important role in the regulation of various genes involved in cell growth, development and the maintenance of body homeostasis. They are closely linked to different human diseases, particularly in cancers. Amplification and overexpression of some miRNAs that are called ‘oncomiRs’ or down-regulation of tumor suppressor miRNAs are associated with genetic alterations that are sufficient to drive tumorigenesis in humans. Lung cancer is the leading cause of cancer-related deaths worldwide. The high mortality rate of lung cancer is not changed even with recent advances in cancer treatment. Several studies demonstrated that miRNAs are involved in the pathogenesis of lung cancer that they negatively or positively regulate gene and protein expression by acting as oncogenes or tumor suppressors. Objective: This article reviewed the current knowledge on the role of miRNAs and their target genes in lung cancer and discussed the potential use of some miRNAs as novel therapeutic agents in lung cancer. Method: Firstly, we collected and summarized all research and review and research articles in databases including Scopus and PubMed. Then, we used related keywords that are important to lung cancer target therapy and their diagnostic and prognostic values. Results: Based on collected articles and research, recognizing critical microRNA and controlling the expression of this microRNA by antagonist oligonucleotides like antagomiRs or anti-miRs and microRNA mimicking will have a remarkable role in treating lung cancer. Conclusion: Many research studies have shown that a combination of chemotherapy plus knockdown or mimicking microRNA is effective and useful in the cancers treatment like lung cancer.

Introduction: Carbapenems are a broad-spectrum class of beta-lactam antibiotics, which are used in treatment of multi-drug resistant infections. Unfortunately, global emerging and spreading of carbapenemase, especially New Delhi metallo β lactamase 1 (blaNDM-1), is a concern in the treatment of multi drug-resistant agents. Here, we report the appearance of blaNDM-1producing Escherichia coli (E. coli) in Iran for the first time. Case Presentation: In this study, 2 blaNDM-1producing E. coli strains were isolated from 2 burn wounds of patients in the Motahari hospital, Tehran. The isolates were resistant to carbapenems (imipenem, meropenem and ertapenem) and other common antibiotics except nitrofurantoin. Combined Disk Test showed that the isolates could not produce blaAmpC and blaKPC carbapenemase, whereas they can produce metallo-β-lactamases (MBL). However, genetic detection using Polymerase Chain Reaction amplification with specific primers for blaKPC, blaIMP, blaVIM-1, blaVIM-1 – blaVIM-37, and blaNDM-1genes showed that only the blaNDM-1gene is amplified from the resistant isolates. Further sequencing of PCR products confirmed the presence of the blaNDM-1gene in these isolates. Conclusions: The emerging of blaNDM-1producing E. coli is a new threat for to the health system in Iran, due to the spreading of the blaNDM-1gene among pathogenic bacteria, which resulted in the emergence of multi drug resistant photogenes. Therefore, early identification of these isolates is mandatory.

CD24 is a heavy glycosylated protein that is overexpressed in numerous cancer and cancer stem cells. It is involved in the development, invasion, and metastasis of the cancer cells. CD24 can be considered in targeted cancer therapy as a new target. Here, phage display technology was used for the identification of novel scFv antibodies against CD24. To do so, the CD24 protein was expressed and purified from a stable transgenic CHO cell line. The cells were developed by using a CD24 encoding construct, which targets the 18S rRNA gene. The recombinant CD24 was used in the biopanning process. Four rounds of biopanning were performed with the Tomlinson J library. The polyclonal phage ELISA and DNA sequencing of the selected colonies confirmed that specific binders have been enriched during the biopanning process. Based on the DNA sequencing results, three phage-displaying scFv were obtained and their specificity to CD24 was verified in the monoclonal phage ELISA. The results showed that clone 3 (called Jd3) has the highest affinity to CD24 and also is the most abundant clone (80%) among the three clones. Therefore, Jd3 was selected for further analyses. In order to produce soluble Jd3-scFv, the phage was transfected to E. coli BL21 pLysS. Soluble Jd3 scFv was expressed and purified successfully. The soluble Jd3 scFv showed appropriate affinity to recombinant CD24 in the ELISA analysis. Also, the immunocytochemistry experiment showed that the purified Jd3 scFv can bind to the CD24 expressing A549 cells. So, the scFv may be useful in the targeted delivery of drugs or diagnostic nanoparticles to the CD24 expressing cancer cells. To the best of our knowledge, this study is the first report to identify an scFv antibody against CD24, using the phage display method.

Todays, after four decades from the discovery of monoclonal antibodies by Kohler and Milstein in 1975, a dozen of antibodies are used in cancer targeted therapy with different strategies. The success of these antibodies depends on the specificity of antigens expressed on the cancer cells. Epithelial Cell Adhesion Molecule (EpCAM), a homophilic cell-cell adhesion glycoprotein is a well- known tumor antigen, which expresses on epithelial tumors and circulating tumor cells as well as cancer stem cells. The EpCAM signaling pathway is associated with proliferation, differentiation and adhesion of epithelial cancer cells. Here we review EpCAM structure, expression profile and its signaling pathway in cancer cells. In addition, we focused on structure, mechanism of action and success of anti EpCAM antibodies which have been used in different clinical trials. Based on literatures, Edrecolomab showed limited efficacy in the phase III studies. The wholly human monoclonal antibody Adecatumumab is dose- and target-dependent in metastatic breast cancer patients expressing EpCAM. The chimeric antibody, Catumaxomab, has been approved for the treatment of malignant ascites; however, this Mab showed considerable results in intrapleural administration in cancer patients. Anti EpCAM toxin conjugated antibodies like, Oportuzumab Monatox (scFv antibody and Pseudomonas exotoxin A (ETA)), Citatuzumab Bogatox (Fab fragment with bouganin toxin) and immono-conjugate antibody Tucotuzumab (monoclonal antibody with IL2), have shown acceptable results in different clinical trials. Almost, all of the antibodies were well-tolerated; however, still more clinical trials are needed for the approval of antibodies for the treatment of specific tumors.

CD24 (cluster of differentiation 24) is a small heavy glycosylated protein, which is overexpressed in many cancer and some cancer stem cells and is associated with the development, invasion, and metastasis of cancer cells. The exact role of CD24 in these processes is not fully understood, however, in this article, it has been tried to present a collection of cancer-related mechanisms attributed to CD24. Based on the literature, CD24 dis-regulates different signaling pathways in various cancer cells, including; Src kinases, STAT3, EGFR, Wnt/β-catenin and MAPK. Src kinases play an important role in the signaling pathways which activate p38 MAPK and STAT3 pathways. Akt and ERK are downstream effectors of CD24-activated EGFR, which promote cell proliferation, invasion and metastasis. CD24 increases the expression of HER2 by the activation of NF-κB transcription factor. Moreover, CD24 up-regulates the expression of miR-21 oncomir through the activation of Src kinases. Identification of the details of these pathways and also new pathways will help researchers to explore new CD24 targeted therapies.

Background Helicobacter pylori is an important pathogen of human gastric mucosa. Antibiotic resistance, especially resistance to clarithromycin is a major factor for treatment failure of H. pylori infections. The main mechanism of clarithromycin resistance in these bacteria is related to point mutations in three different locations of 23S rRNA gene. Objectives The aims of this study were to evaluate the resistance rate to clarithromycin among local H. pylori isolates by the E-test method and to determine the profile of point mutation in 23S rRNA by real-time polymerase chain reaction (PCR) method. Patients and Methods Eighty biopsy samples were collected from dyspeptic patients by endoscopy during 2011 - 2012. All samples were homogenized immediately and cultured on supplemented brucella blood agar and incubated under microaerophilic conditions. Further biochemical tests and ureC gene PCR was done for H. pylori confirmation. The H. pylori OC1096 strain was used as the control strain, simultaneously. Frequency of clarithromycin resistance was determined by the E-test method based on the clinical and laboratory standard institute (CLSI) standards. Point mutation profile was determined by real-time PCR and further analysis of melting curve, amplicon sequencing was done continuously. Results From 80 biopsy samples, 20 positive H. pylori isolates were detected and confirmed by biochemical tests and PCR method. Overall, 21.7% of the H. pylori isolates, showed clarithromycin resistance phenotype by use of the E-test. Also, the minimal inhibitory concentration of clarithromycin was determined as ≥ 0.5 mg/L by the E-test method. Only point mutation in the location of A2143G with melting temperature of 54.7°C was observed in all resistant isolates. Conclusions This study showed that the frequency of H. pylori clarithromycin resistance in Iran is relatively high. Since clarithromycin is not commonly used in Iran for H. pylori eradication, the high rate of resistance could be related to cross-reactivity between other macrolides. Therefore, macrolide antibiotics must be prescribed with precaution in any case of treatment other than H. pylori infections. All resistant isolates showed A2143G mutation in 23S rRNA as the dominant pattern of point mutation at least in Tehran H. pylori isolates.