Echinococcus granulosus sheep strain (G1) as the predominant genotype in definitive host (dogs) isolates in northeastern Iran.

Echinococcus granulosus sensu lato (E. granulosus s.l.) is a zoonotic parasite, causing cystic echinococcosis in humans. In the present study, prevalence and genotypes of E. granulosus s.l. was assessed in stools collected from 244 dogs including 138 stray and 106 domestic animals using high resolution melting curve (HRM) method. Initially, to detect taeniid eggs in feces, all samples were examined using the formalin-ether techniques. Genomic DNA was extracted from the positive samples and E. granulosus s.l. was differentiated from other Taeniidae parasites using SSU-rDNA gene and E. granulosus s.l. was analyzed for genotyping using HRM based on the cox1 gene. In total, 12.7% (31/244) of the samples were positive for Taeniidae eggs. In addition, among the positive samples, 77.4% (24/31) were positive for E. granulosus s.l.. In details, 11.3% (12/106) of the domestic dogs and 8.7% (12/138) of the stray dogs were positive for E. granulosus s.l.. The results of HRM analysis showed that all E. granulosus s.l. isolates were G1 strain. Findings of the present study indicated a considerable prevalence of E. granulosus G1 among dogs in the northeast of Iran and imply a serious risk of transmitting to humans and livestock.

Combined Treatment of Dendrosomal-Curcumin and Daunorubicin Synergistically Inhibit Cell Proliferation, Migration and Induce Apoptosis in A549 Lung Cancer Cells.

Purpose: Chemotherapy drugs used to treat lung cancer are associated with drug resistance and severe side effects. There have been rising demands for new therapeutic candidates and novel approaches, including combination therapy. Here, we aimed to investigate the combinatorial effect of a dendrosomal formulation of curcumin (DNC) and daunorubicin (DNR) on the A549 lung cancer cell line. Methods: We performed cytotoxicity, apoptosis, cell migration, colony-formation capacity, and gene expression analysis to interpret the mechanism of action for a combination of DNC and DNR on A549 cells. Results: Our results revealed that the combination of DNC and DNR could synergistically inhibit the A549 cells' growth. This synergistic cytotoxicity was further approved by flow cytometry, migration assessment, colony-forming capacity and gene expression analysis. DNR combination with DNC resulted in increased apoptosis to necrosis ratio compared to DNR alone. In addition, the migration and colony-forming capacity were at the minimal range when DNC was combined with DNR. Combined treatment decreased the expression level of MDR-1, hTERT and Bcl-2 genes significantly. In addition, the ratio of Bax/Bcl2 gene expression significantly increased. Our analysis by free curcumin, dendrosomes and DNC also showed that dendrosomes do not have any significant cytotoxic effect on the A549 cells, suggesting that this carrier has a high potential for enhancing the curcumin's biological effects. Conclusion: Our observations suggest that the DNC formulation of curcumin synergistically enhances the antineoplastic effect of DNR on the A549 cell line through the modulation of apoptosis/necrosis ratio, as well as Bax/Bcl2 ratio, MDR-1 and hTERT gene expression.

Diagnostic accuracy of cerebrospinal fluid and serum-isolated extracellular vesicles for glioblastoma: a systematic review and meta-analysis.

BACKGROUND: Glioblastoma (GBM) is the most malignant brain cancer because there are no available biopsy-free methods for the diagnosis or the preoperative early detection. In this regard, the development of a non- or minimally invasive methods for early detection could increase the survival rate of GBM patients. METHODS: The present study aimed to assess the diagnostic accuracy of extracellular vesicles (EVs) derived RNAs, isolated from patients' CSF or serum for GBM diagnosis. For this purpose, we searched all literature databases and performed a backward and forward reference checking procedure to retrieve appropriate studies. We conducted a meta-analysis on EVs derived biomarkers as well as sensitivity analysis and meta-regression. RESULTS: We identified EVs-derived 24 RNAs, which can diagnose GBM. The analyzed pooled data showed 76% sensitivity, 80% specificity, and 0.85 AUC, for 16 biomarkers. Besides, the pooled PLR, NLR, and DOR were 3.7, 0.30, and 12, respectively. Subgroup analysis did not show a significant difference between serum and CSF. CONCLUSIONS: According to the pooled sensitivity, specificity, and AUC for EVs derived biomarkers, we suggest that EVs-derived biomarkers might serve as a high potential and noninvasive diagnostic tool for GBM detection using serum and CSF samples.

Designer Exosomes: A New Platform for Biotechnology Therapeutics.

Desirable features of exosomes have made them a suitable manipulative platform for biomedical applications, including targeted drug delivery, gene therapy, cancer diagnosis and therapy, development of vaccines, and tissue regeneration. Although natural exosomes have various potentials, their clinical application is associated with some inherent limitations. Recently, these limitations inspired various attempts to engineer exosomes and develop designer exosomes. Mostly, designer exosomes are being developed to overcome the natural limitations of exosomes for targeted delivery of drugs and functional molecules to wounds, neurons, and the cardiovascular system for healing of damage. In this review, we summarize the possible improvements of natural exosomes by means of two main approaches: parental cell-based or pre-isolation exosome engineering and direct or post-isolation exosome engineering. Parental cell-based engineering methods use genetic engineering for loading of therapeutic molecules into the lumen or displaying them on the surface of exosomes. On the other hand, the post-isolation exosome engineering approach uses several chemical and mechanical methods including click chemistry, cloaking, bio-conjugation, sonication, extrusion, and electroporation. This review focuses on the latest research, mostly aimed at the development of designer exosomes using parental cell-based engineering and their application in cancer treatment and regenerative medicine.

Improvement, scaling-up, and downstream analysis of exosome production.

Exosomes are the most researched extracellular vesicles. In many biological, physiological, and pathological studies, they have been identified as suitable candidates for treatment and diagnosis of diseases by acting as the carriers of both drugs and genes. Considerable success has been achieved regarding the use of exosomes for tissue regeneration, cancer diagnosis, and targeted drug/gene delivery to specific tissues. While major progress has been made in exosome extraction and purification, extraction of large quantities of exosomes is still a major challenge. This issue limits the scope of both exosome-based research and therapeutic development. In this review, we have aimed to summarize experimental studies focused at increasing the number of exosomes. Biotechnological studies aimed at identifying the pathways of exosome biogenesis to manipulate some genes in order to increase the production of exosomes. Generally, two major strategies are employed to increase the production of exosomes. First, oogenesis pathways are genetically manipulated to overexpress activator genes of exosome biogenesis and downregulate the genes involved in exosome recycling pathways. Second, manipulation of the cell culture medium, treatment with specific drugs, and limiting certain conditions can force the cell to produce more exosomes. In this study, we have reviewed and categorized these strategies. It is hoped that the information presented in this review will provide a better understanding for expanding biotechnological approaches in exosome-based therapeutic development.

Renal echinococcosis; the parasite, host immune response, diagnosis and management.

Renal echinococcosis is a rare parasite-caused disease of humans and animals; it makes up about 4% of confirmed cases of cystic echinococcosis. It is a zoonotic disease that occurs in the intermediate hosts harboring the larval stage, the hydatid cyst, of Echinococcus spp. The renal involvement is often asymptomatic or with unspecific signs. Its diagnosis is mostly based on imaging technique. Immunodiagnostic tests are not applicable. Furthermore, because the disease is not common, our knowledge about its different aspects is scarce. In this review, the parasite, host immune response, diagnosis, and management of renal echinococcosis are described.

The relationship between molecular content of mesenchymal stem cells derived exosomes and their potentials: Opening the way for exosomes based therapeutics.

At least, more than half of our understanding of extracellular vesicles owes to the studies conducted over the past few years. When it became clear that the exosomes have various potentials in medicine, extensive research has focused on these potentials in a variety of areas including cancer, drug delivery and regenerative medicine. The growing understanding of molecular structure and functions of exosomes causes the vision to become brighter in the exosomes complexity, and our attitude toward these vesicles has undergone changes accordingly. Proteomic and transcriptomic studies on exosomes have highlighted their molecular diversity. In this review, we explicitly examine the exosomes composition, molecular structure and their therapeutic potentials in some diseases. Due to the very heterogeneous nature of exosomes, the process of their use as a therapeutic agent in the clinic has been challenged. We are still at the beginning of recognizing the molecular composition of exosomes and mechanisms that affect their physiology and biology. The growing trend of engineering of exosomes has shown a promising future to further utilize them in a different field. Molecular profiling of exosomes and their content for their related potentials in regenerative medicine should be done exactly for further defining a minimum content for specific therapeutic potentials.

Albendazole and Treatment of Hydatid Cyst: Review of the Literature.

Human hydatid cyst or cystic echinococcosis is a life-threatening zoonotic disease that occurs in most countries worldwide and is recognized as a major public health problem. Following ingestion of Echinococcus granulosus eggs, hydatid cysts which are the larval stage of the worm are formed mostly in liver and lungs, and occasionally in other organs of human. The usual treatment for hydatid cyst is open surgery. One of the problems following surgery is the recurrence. In the last decades, albendazole has been used for the treatment of hydatid cyst. This drug can be used alone or jointly with surgical procedures. However, its efficacy has not been well documented. Thus, in this work, the treatment of hydatid cyst with albendazole in different investigations including case studies, clinical trials in human and experimental works in animals has been reviewed. According to the findings of this review, it can be concluded that treatment of hydatid cyst with albendazole may be associated with the prevention of recurrence and reduction of the size and death of the hydatid cysts.

Th1/Th2-type cytokine profile in C57 black mice inoculated with live Echinococcus granulosus protoscolices.

BACKGROUND AND OBJECTIVE: Cystic echinococcosis (CE) is a widespread parasitic disease caused by infection with the larval stage of a tapeworm, Echinococcus granulosus. The immune response to hydatid cyst in intermediate hosts is a complex and contradictory issue. It is suggested that a Th2 response would favor the establishment of the parasite, whereas a Th1 response would be lethal for the parasite. Thus, the aim of the present study was to evaluate the levels of IL2, TNFα, and IFNγ as T helper (Th)1-type cytokines, IL4 as a Th2-type cytokine, and total IgG in C57/black mice inoculated with E. granulosus protoscoleces (PSCs). MATERIALS AND METHOD: In this experimental study, six C57/black mice were intraperitoneally inoculated with live E. granulosus PSCs and a control group consist of six C57/black mice received normal saline. The quantitative concentrations of IL2, TNFα, IFNγ, and IL4 were determined in the first, second, fourth, eighth and 12th-week post inoculation in both case and control groups. RESULTS: The results showed that at the early post-infection phase (3-4 weeks) the Th1-type cytokine profile was predominant, however the shift to Th2-type cytokine took place in the 4th week. CONCLUSION: Based on the results of the present study, we can suggest that the shift from Th1 to Th2 reactivity may be associated with persistent of the disease because Th2 reactivity may be less effective than Th1 reactivity in countering the parasite.

Effect of two hydatid cyst antigens on the growth of melanoma cancer in C57/black mice.

Hydatid cyst is the larval stage of Echinococcus granulosus. In previous studies inhibitory effect of this parasite on cancer cell growth in culture medium has been shown. In this study effect of hydatid cyst antigens on tumor growth in experimental animals has been investigated. Two antigens of hydatid cyst including protoscolices excretory secretory antigen and hydatid fluid absorbed on alum as adjuvant were injected to two groups of C57/black mice as case groups. Control groups were injected with only saline and alum. All mice then were injected with melanoma cells. Both antigens reduced the tumor size in mice in case groups. The difference of tumor size in mice in case groups and control group was statistically significant. In conclusion, anti-tumor effect of hydatid cyst antigens may be related to antigenic similarities which exist between hydatid cyst and cancer cells.

IL-4 gene expression in adventitial layer (fibrous layer) of hepatic ovine and bovine hydatid cysts.

Cystic Echinococcosis is a parasitic disease with cosmopolitan distribution caused by the tape worm Echinococcus granulosus. Fibrous layer is developed around the cyst as a host immune response reaction. The aim of this study was to evaluate the rate of IL-4 gene expression in fibrous layer of bovine and ovine hepatic hydatid cysts using quantitative technique of Real-Time PCR. In this descriptive study the samples of hydatid cyst fibrous layer were taken from 6 bovine and 6 ovine hepatic hydatid cysts. Samples of normal liver tissue close to the cyst were also taken as controls. Total RNA from each sample was extracted and then converted to cDNA. Afterward, the rate of IL-4 gene expression for each sample was evaluated using real-time PCR technique. Data were analyzed by REST software (version 2.0.13, 2009). In sheep the rate of IL-4 gene expression in the fibrous layer of hepatic hydatid cysts was 1.98 times more than the rate of IL4 gene expression in control samples, but the difference was not significant (P = 0.561). In cattle the rate of IL-4 gene expression in the fibrous layer of hepatic hydatid cysts was 9.84 times more than that of control samples which was statistically significant (P < 0.001). With high rate of IL4 expression especially in fibrous layer of bovine hydatid cyst, it can be concluded that this interleukin may play an important role in host parasite relationship.

Parasites and immunotherapy: with or against?

Immunotherapy is a sort of therapy in which antibody or antigen administrates to the patient in order to treat or reduce the severity of complications of disease. This kind of treatment practiced in a wide variety of diseases including infectious diseases, autoimmune disorders, cancers and allergy. Successful and unsuccessful immunotherapeutic strategies have been practiced in variety of parasitic infections. On the other hand parasites or parasite antigens have also been considered for immunotherapy against other diseases such as cancer, asthma and multiple sclerosis. In this paper immunotherapy against common parasitic infections, and also immunotherapy of cancer, asthma and multiple sclerosis with parasites or parasite antigens have been reviewed.