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Background: Coronavirus disease 2019 (COVID-19) has become one of the most serious diseases worldwide. The contagiousness of the virus and its unexpectedly rapid spread in different communities have raised many concerns. Objectives: This study investigated the association of clinical findings and hospital stay length of COVID-19 patients with diabetes and hypertension history in Garmsar Hospital. Methods: This cross-sectional study assessed COVID-19 patients admitted to Motamedi Hospital, Garmsar, Iran. Data were recorded in Minitab V17 software and analyzed through analysis of variance (ANOVA). Pearson's and Spearman's correlation coefficients were also computed for quantitative and qualitative variables, respectively. Results: The mean age was significantly higher in the group with underlying diseases than in the control group. The proportion of CRP-positive cases was higher in the hypertensive group than in the diabetes + hypertensive group, but it was not statistically significant. The rate of shortness of breath, length of hospital stay, and mortality were lower in the control group than in the group with underlying diseases, but this difference was not statistically significant. Conclusions: Although the incidence of respiratory distress, the length of hospital stay, and the mortality rate were lower in the control group than in the group with diabetes + hypertension, there was no significant association between these conditions and the risk of death and the length of hospital stay due to COVID-19. [ABSTRACT FROM AUTHOR]

Objective: Asthma, a chronic inflammatory disease with diverse pathomechanisms, presents challenges in developing personalized diagnostic and therapeutic approaches. This review aims to provide a comprehensive overview of the role of exosomes, small extracellular vesicles, in asthma pathophysiology and explores their potential as diagnostic biomarkers and therapeutic tools. Methods: A literature search was conducted to identify recent studies investigating the involvement of exosomes in asthma. The retrieved articles were analyzed to extract relevant information on the role of exosomes in maintaining lung microenvironment homeostasis, regulating inflammatory responses, and their diagnostic and therapeutic potential for asthma. Results: Exosomes secreted by various cell types, have emerged as crucial mediators of intercellular communication in healthy and diseased conditions. Evidence suggest that exosomes play a significant role in maintaining lung microenvironment homeostasis and contribute to asthma pathogenesis by regulating inflammatory responses. Differential exosomal content between healthy individuals and asthmatics holds promise for the development of novel asthma biomarkers. Furthermore, exosomes secreted by immune and nonimmune cells, as well as those detected in biofluids, demonstrate potential in promoting or regulating immune responses, making them attractive candidates for designing new treatment strategies for inflammatory conditions such as asthma. Conclusion: Exosomes, with their ability to modulate immune responses and deliver therapeutic cargo, offer potential as targeted therapeutic tools in asthma management. Further research and clinical trials are required to fully understand the mechanisms underlying exosome‐mediated effects and translate these findings into effective diagnostic and therapeutic strategies for asthma patients. [ABSTRACT FROM AUTHOR]

The treatment of osteosarcoma, as the most destructive bone cancer, is allied with many challenges. One of the new tissue engineering approaches is the use of a local drug delivery system implanted after surgery. This system can be a scaffold mimicking the natural tissue extracellular matrix, loaded with drugs. Therefore, the purpose of this study was to construct different berberine-loaded nano-hydroxyapatite/gelatin scaffolds, and to investigate their effects on osteosarcoma cancer cells. The scaffolds after fabrication were analyzed for physicochemical properties using XRD, EDS, FTIR, and FE-SEM. The drug loading and release, and the biocompatibility (MTT and LDH) were also evaluated. Moreover, apoptosis, viability, colony formation, and scratch tests were conducted on cancer cells. The scaffolds exhibited a porosity of 66.64% with pore sizes of 10–70 micrometers. The results showed that the released berberine had a cytotoxic effect on cancer cells (cell death of ∼38–80% based on LDH, and cell proliferation <56% and <21% in terms of early and late exposure based on MTT). The apoptosis results revealed a remarkable increase in the percentage of apoptotic MG63 cells after treatment with berberine-loaded scaffolds in a dose-dependent manner. All scaffolds with berberine were able to significantly prevent colony formation and cell migration (only 9.7–15.7% closure). [ABSTRACT FROM AUTHOR]

In this research chemical composition and antimicrobial effects of Elaeagnus angustifolia L. (E. angustifolia L.) whole fruit ethanolic extract was investigated on common pathogenic microorganisms (Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, and Candida albicans). The phytochemical composition of E. angustifolia was screened by Gas Chromatography-Mass Spectrometry (GC/MS). The minimum inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) of the extract were determined using the broth dilution technique. According to the results, 13 major compounds such as flavonoid, aldehyde, alcoholic and fatty acids were identified by GC/MS. In addition, the extract could inhibit the growth of all examined pathogenic strains. The MIC was 3.75 to 1.87 mg ml-1 while maximum activity was found against Staphylococcus aureus. Besides, the MBC was ranging from 7.5 to 3.75 mg ml-1. Since E. angustifolia whole fruit ethanolic extract contains phytochemical compounds and has antimicrobial potential it can be recommended as a natural active agent for application in the food industry. [ABSTRACT FROM AUTHOR]

In this study, the biological activities of whole herb extract of a medicinal plant named Smirnovia Iranica were investigated. The extraction was performed using Supercritical CO2 and phytochemical compounds, total phenolic content (TPC), total flavonoid content (TFC), antioxidant, anti-bacterial, and anti-cancer effect were determined in the extract. Based on the results, high TPC concentration (120.36 mg GAE/100 g FW) and TFC (17.41 mg quercetin/100g FW) were obtained in the extract. Besides, the extract showed significant antioxidant activity (IC50=53.97 µg mL-1). Moreover, the extract showed a notable inhibitory effect against Escherichia coli (MIC=15.63 mg mL-1) and Salmonella enterica (MIC=31.25 mg mL-1). On the other hand, this extract showed the cytotoxic effect on glioblastoma cancer cell lines in the MTT assay. This is the first, yet comprehensive, scientific report about the chemical composition and pharmacological properties of the extract of Smirnovia Iranica whole herb. According to current results, the Smirnovia Iranica extract has excellent antioxidant properties for application as bioactive components for various objects such as as food supplements. The experiment confirmed the efficacy of the extracts as natural antimicrobials and suggested the possibility of employing them in drugs for the treatment of infectious diseases caused by the test organisms. [ABSTRACT FROM AUTHOR]

Introduction: Alumina-titanium (Al2O3-Ti) composites with enhanced mechanical and corrosion properties have been recently developed for potential applications in orthopaedics and hard tissue replacements. However, before any clinical use, their interactions with biological environment must be examined. Methods: The aim of this study, therefore, was to assess the biocompatibility of three Al2O3-Ti composites having 25, 50, and 75 volume percentages of titanium. These materials were made by spark plasma sintering (SPS), and MC3T3-E1 cells were cultured onto the sample discs to evaluate the cell viability, proliferation, differentiation, mineralization, and adhesion. Furthermore, the apatite formation ability and wettability of the composites were analysed. Pure Ti (100Ti) and monolithic Al2O3 (0Ti) were also fabricated by SPS and biological characteristics of the composites were compared with them. Results: The results showed that cell viability to 75Ti (95.0%), 50Ti (87.3%), and 25Ti (63.9%) was superior when compared with 100Ti (42.7%). Pure Al2O3 also caused very high cell viability (89.9%). Furthermore, high cell proliferation was seen at early stage for 50Ti, while the cells exposed to 75Ti proliferated more at late stages. Cell differentiation was approximately equal between different groups, and increased by time. Matrix mineralization was higher on the composite surfaces rather than on 0Ti and 100Ti. Moreover, the cells adhered differently to the surfaces of different biomaterials where more spindle-shaped configuration was found on 100Ti, slightly enlarged cells with dendritic shape and early pseudopodia were observed on 75Ti, and more enlarged cells with long dendritic extensions were found on 0Ti, 25Ti, and 50Ti. The results of EDS analysis showed that both Ca and P deposited on the surfaces of all materials, after 20 days of immersion in SBF. Conclusion: Our in-vitro findings demonstrated that the 75Ti, 50Ti, and 25Ti composites have high potential to be used as load-bearing orthopedic materials. [ABSTRACT FROM AUTHOR]

Elaeagnus. angustifolia L. (EA) is a natural plant food with therapeutic and medicinal properties for treating various diseases such as rheumatoid arthritis and osteoporosis. Since herbal agents are origins of bioactive compounds, they can be applied in complementary treatment protocols. In this study, EA whole fruit extract's cytotoxic effects were investigated on both animal and human glioblastoma cancer cell lines. The extract of whole fruit of EA was obtained by maceration in ethanol. The phytochemical compounds were identified using high-performance liquid chromatography (HPLC). The MTT and LDH assays were performed to evaluate the cytotoxicity effect of the extract and the determination of cell death. Wound-healing assay and colony formation analysis were employed for migration and proliferation evaluation. Based on HPLC analysis, the main flavonoid components of the extract were included rutin and apigenin. The results demonstrated that EA extract at the dose of 125 to 2000 µg/ml and 61.5 to 2000 µg/ml inhibited C6 and U87 cells' viability and induced significant cell cytotoxicity at both 48 and 72 h incubation times. Besides, EA extract significantly inhibited cell migration and colony formation at 250 to 1000 µg/ml concentration. Overall, the results showed that EA extract could inhibit several stages in glioblastoma carcinogenesis in vitro. Therefore, it can be suggested as an anticancer in the clinical treatment approaches of glioblastoma cancer. [ABSTRACT FROM AUTHOR]

Recent studies suggest that Spirulina may have great therapeutic benefits due to its antioxidant and anti‐inflammatory properties. The primary objective of this study was to evaluate the chemopreventive properties of the Spirulina microalgae (Spi) on the regression and survival of tumor, histopathological features of glioblastoma, and detection of the molecular mechanism of Spi. Tumor viability versus Spi was determined using the MTT assay. In vivo antitumor activity of Spi was studied using the glioblastoma model. After tumor induction, the animals were euthanized, and their brains were removed. Histological evaluation was performed for tumor size and manifestation. The mechanisms of the anticancer effects of Spi were investigated by evaluating the microRNAs and their targets. The results demonstrated that Spi inhibited C6 and U87 cell proliferation and induced cell death. Histopathologic results showed that the administration of Spi could delay the development of tumors and prolonged the survival of tumor‐bearing animals. Furthermore, Spi significantly upregulated miR‐34a and miR‐125b that have a key role in the progression of PI3K/AKT/mTOR pathway. This is the first in vivo report on the chemo‐preventive effect of Spi against glioblastoma, suggesting its potential use in the chemoprevention of this cancer and the antiglioma molecular mechanism of Spi. [ABSTRACT FROM AUTHOR]

Background: Alumina-titanium (Al2O3-Ti) biocomposites have been recently developed with improved mechanical properties for use in heavily loaded orthopedic sites. Their biological performance, however, has not been investigated yet. Methods: The aim of the present study was to evaluate the in vivo biological interaction of Al2O3-Ti. Spark plasma sintering (SPS) was used to fabricate Al2O3-Ti composites with 25 vol.%, 50 vol.%, and 75 vol.% Ti content. Pure alumina and titanium were also fabricated by the same procedure for comparison. The fabricated composite disks were cut into small bars and implanted into medullary canals of rat femurs. The histological analysis and scanning electron microscopy (SEM) observation were carried out to determine the bone formation ability of these materials and to evaluate the bone-implant interfaces. Results: The histological observation showed the formation of osteoblast, osteocytes with lacuna, bone with lamellar structures, and blood vessels indicating that the healing and remodeling of the bone, and vasculature reconstruction occurred after 4 and 8 weeks of implantation. However, superior bone formation and maturation were obtained after 8 weeks. SEM images also showed stronger interfaces at week 8. There were differences between the composites in percentages of bone area (TB%) and the number of osteocytes. The 50Ti composite showed higher TB% at week 4, while 25Ti and 75Ti represented higher TB% at week 8. All the composites showed a higher number of osteocytes compared to 100Ti, particularly 75Ti. Conclusions: The fabricated composites have the potential to be used in load-bearing orthopedic applications. [ABSTRACT FROM AUTHOR]

Dendritic cells are important in initiating immune responses; therefore, a range of dendritic cell--based approaches have been established to induce immune response against cancer cells. However, the presence of immunosuppressive mediators such as adenosine in the tumor microenvironment reduces the efficacy of dendritic cell--based cancer immunotherapy. In this study, we investigated whether blockade of the A2A adenosine receptor with a selective antagonist and a CD73 inhibitor may increase the efficacy of a dendritic cell--based cancer vaccine. According to the findings, this therapeutic combination reduced tumor growth, prolonged survival of tumor-bearing mice, and enhanced specific antitumor immune responses. Thus, we suggest that targeting cancer-derived adenosine improves the outcomes of dendritic cell--based cancer immunotherapy. [ABSTRACT FROM AUTHOR]

The innate immune system utilizes pattern recognition receptors (PRRs) to recognize microbes. Pathogens contain various molecules with diverse effects on immune response. In this study, we evaluated the effect of DNA and protein components derived from two intracellular microorganisms including Listeria monocytogenes (L. monocytogenes) and Toxoplasma gondii (T. gondii) on dendritic cells (DCs) activation and ensuing adaptive immune responses. DNA and protein components of L. monocytogenes and T. gondii were prepared using relevant kits. DNA and protein components of these two pathogens were added to immature DCs (iDCs). Subsequently, co-stimulatory expression and cytokine production by DCs were measured. Finally, we evaluated the stimulatory capacity of mature DCs (mDCs) in DC-T cells co-culture. The results showed that protein matured-DCs produced higher level of IL (Interleukin)-12p70. There was also a significant increase in Interferon-Gamma (IFN-γ) production and proliferative capacity in T cells co-cultured with protein matured-DCs. On the other hand, DNA matured-DCs produced significantly higher amounts of Transforming growth factor-beta (TGF-β). Collectively, these results imply a regulatory nature for DNA and potent stimulatory character for protein components of these two intracellular microorganisms. [ABSTRACT FROM AUTHOR]

Objectives: The biological performance of aluminum oxide-titanium (Al2O3-Ti) composites requires special attention to achieve improved osteoblastic differentiation, and subsequent osseointegration/strong anchorage with the surrounding bone. Therefore, the aim of this study was to improve them by providing calcium phosphate (Ca-P)/bovine serum albumin (BSA) coating on their surfaces., Methods: Ca-P/BSA coatings were prepared on the surfaces of 75vol.%Ti composites (75Ti-BSA) and pure Ti (100Ti-BSA as a control). The surface characteristics, phase analysis, micro-hardness, BSA release profile and biological responses including cytotoxicity, cell viability, differentiation, mineralization, and cell adhesion were evaluated., Results: The results showed that lower cytotoxicity% and higher mitochondrial activity or viability % were associated with the samples with Ca-P/BSA coatings (particularly 75Ti-BSA having 21.3% cytotoxicity, 111.4% and 288.6% viability at day 1 and 7, respectively). Furthermore, the Ca-P/BSA coating could highly enhance the differentiation of pre-osteoblast cells into osteoblasts in 75Ti-BSA group (ALP concentration of 4.8 ng/ml). However, its influence on cell differentiation in 100Ti-BSA group was negligible. Similar results were also obtained from mineralization assay. The results on cell adhesion revealed that the Ca-P/BSA coated samples differently interacted with MC3T3-E1 cells; enlarged flat cells on 75Ti-BSA vs more spindle-shaped cells on 100Ti-BSA., Conclusions: Ca-P/BSA coated Al2O3-Ti provided promising biological performance, superior to that of uncoated composites. Therefore, they have the potential to improve implant osseointegration., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Introduction: Alumina-titanium (Al 2 O 3 -Ti) composites with enhanced mechanical and corrosion properties have been recently developed for potential applications in orthopaedics and hard tissue replacements. However, before any clinical use, their interactions with biological environment must be examined. Methods: The aim of this study, therefore, was to assess the biocompatibility of three Al 2 O 3 -Ti composites having 25, 50, and 75 volume percentages of titanium. These materials were made by spark plasma sintering (SPS), and MC3T3-E1 cells were cultured onto the sample discs to evaluate the cell viability, proliferation, differentiation, mineralization, and adhesion. Furthermore, the apatite formation ability and wettability of the composites were analysed. Pure Ti (100Ti) and monolithic Al 2 O 3 (0Ti) were also fabricated by SPS and biological characteristics of the composites were compared with them. Results: The results showed that cell viability to 75Ti (95.0%), 50Ti (87.3%), and 25Ti (63.9%) was superior when compared with 100Ti (42.7%). Pure Al 2 O 3 also caused very high cell viability (89.9%). Furthermore, high cell proliferation was seen at early stage for 50Ti, while the cells exposed to 75Ti proliferated more at late stages. Cell differentiation was approximately equal between different groups, and increased by time. Matrix mineralization was higher on the composite surfaces rather than on 0Ti and 100Ti. Moreover, the cells adhered differently to the surfaces of different biomaterials where more spindle-shaped configuration was found on 100Ti, slightly enlarged cells with dendritic shape and early pseudopodia were observed on 75Ti, and more enlarged cells with long dendritic extensions were found on 0Ti, 25Ti, and 50Ti. The results of EDS analysis showed that both Ca and P deposited on the surfaces of all materials, after 20 days of immersion in SBF. Conclusion: Our in-vitro findings demonstrated that the 75Ti, 50Ti, and 25Ti composites have high potential to be used as load-bearing orthopedic materials.

Large injuries to bones are still one of the most challenging musculoskeletal problems. Tissue engineering can combine stem cells, scaffold biomaterials, and biofactors to aid in resolving this complication. Therefore, this review aims to provide information on the recent advances made to utilize the potential of biomaterials for making bone scaffolds and the assisted stem cell therapy and use of biofactors for bone tissue engineering. The requirements and different types of biomaterials used for making scaffolds are reviewed. Furthermore, the importance of stem cells and biofactors (growth factors and extracellular vesicles) in bone regeneration and their use in bone scaffolds and the key findings are discussed. Lastly, some of the main obstacles in bone tissue engineering and future trends are highlighted.

Regenerative medicine (RM) is an interdisciplinary field that uses different approaches to accelerate the repair and regeneration or replace damaged or diseased human cells or tissues to achieve normal tissue function. These approaches include the stimulation of the body's own repair processes, transplantation of progenitor cells, stem cells, or tissues, as well as the use of cells and exosomes as delivery-vehicles for cytokines, genes, or other therapeutic agents. COVID-19 pneumonia is a specific disease consistent with diffuse alveolar damage resulting in severe hypoxemia. Therefore, the most serious cause of death from COVID-19 is lung dysfunction. Here, we consider RM approaches to cure COVID-19 pneumonia based on what RM has so far used to treat lung diseases, injuries, or pneumonia induced by other pathogens. These approaches include stem and progenitor cell transplantation, stem cell-derived exosomes, and microRNAs therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Tumor-derived exosomes contain biological contents such as proteins, lipids, RNA (miRNAs, mRNAs, lncRNA), and DNA for intracellular communication. Meanwhile, studies have shown the role of exosomes in cancer progression, metastasis, and therapeutic resistance. Furthermore, tumor exosomes have received growing attention due to their potential as novel therapeutic protocols for the treatment of cancers. Adenosine nucleoside, which is a derivative of ATP, is highly elevated in the tumor microenvironment by CD39 and CD73 enzymatic activity. Recently, it is distinguished that cancer cell-derived exosomes carry CD39 and CD73 on their surface and may contribute to rising adenosine levels in the tumor microenvironment. In this review, we summarize the evidence of CD39/CD73-bearing exosomes and their role in cancer development, progression, invasion, angiogenesis, metastasis and their application in the selection of the appropriate strategy to treat different types of cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Previous studies have demonstrated that maturation of dendritic cells (DCs) by pathogenic components through pathogen-associated molecular patterns (PAMPs) such as Listeria monocytogenes lysate (LML) or CpG DNA can improve cancer vaccination in experimental models. In this study, a mathematical model based on an artificial neural network (ANN) was used to predict several patterns and dosage of matured DC administration for improved vaccination. The ANN model predicted that repeated co-injection of tumor antigen (TA)-loaded DCs matured with CpG (CpG-DC) and LML (List-DC) results in improved antitumor immune response as well as a reduction of immunosuppression in the tumor microenvironment. In the present study, we evaluated the ANN prediction accuracy about DC-based cancer vaccines pattern in the treatment of Wehi164 fibrosarcoma cancer-bearing mice. Our results showed that the administration of the DC vaccine according to ANN predicted pattern, leads to a decrease in the rate of tumor growth and size and augments CTL effector function. Furthermore, gene expression analysis confirmed an augmented immune response in the tumor microenvironment. Experimentations justified the validity of the ANN model forecast in the tumor growth and novel optimal dosage that led to more effective treatment.

Immunotherapy has been introduced into cancer treatment methods, but different problems have restricted the efficacy of these protocols in clinical trials such as the presence of various immunomodulatory factors in the tumor microenvironment. Adenosine is an immunosuppressive metabolite produced by the tumor to promote growth, invasion, metastasis, and immune evasion. Many studies about adenosine and its metabolism in cancer have heightened interest in pursuing this treatment approach. It seems that targeting the adenosine pathway in combination with immunotherapy may lead to efficient antitumor response. In this review, we provide information on the roles of both adenosine and CD73 in the immune system and tumor development. We also describe recent studies about combination therapy with both purinergic inhibitors and other immunotherapeutic methods., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest.

Dendritic cells are important in initiating immune responses; therefore, a range of dendritic cell-based approaches have been established to induce immune response against cancer cells. However, the presence of immunosuppressive mediators such as adenosine in the tumor microenvironment reduces the efficacy of dendritic cell-based cancer immunotherapy. In this study, we investigated whether blockade of the A2A adenosine receptor with a selective antagonist and a CD73 inhibitor may increase the efficacy of a dendritic cell-based cancer vaccine. According to the findings, this therapeutic combination reduced tumor growth, prolonged survival of tumor-bearing mice, and enhanced specific antitumor immune responses. Thus, we suggest that targeting cancer-derived adenosine improves the outcomes of dendritic cell-based cancer immunotherapy.

Introduction: The critical role of regulatory T (Treg) cells in dampening immune responses against tumor cells is apparent. Therefore, several methods have been introduced for eliminating Treg. Among them, inducing immune responses against Treg cells expressing Foxp3 transcription factor is a hopeful approach to decrease the frequency of Tregs. In current study, we used the chimeric FoxP3-Fc(IgG) fusion construct/protein to effectively stimulate the immune responses against Treg cells., Materials and Methods: Previously constructed FoxP3-Fc(IgG) DNA vaccine and its protein counterpart were injected into C57BL/6 mice in a prime/boost regimen. After 2 weeks, the mice were killed to measure the frequency of Tregs in their spleens, as well as analyze their specific cytokine production, T-cell proliferation, and CD8 T-cell cytotoxicity against FoxP3 protein., Results: FACS analysis of FoxP3 CD4 cells in splenocytes revealed the efficiency of FoxP3 DNA-prime protein-boost strategy to decrease the Treg cells and further showed considerable superiority of Fc(IgG) fusion strategy. This significant reduction in Treg frequency was also concomitant with higher FoxP3-specific CTL and Th1 responses in FoxP3-Fc vaccinated animals., Conclusions: Prime/boost vaccination against FoxP3 in addition to enhanced antigen presentation by means of Fc fusion strategy could be successfully considered for Treg depletion studies. Validity of this approach should be experimentally tested in preclinical tumor models.

The use of dendritic cells (DCs) as a cellular adjuvant is a promising approach to the immunotherapy of cancer. It has previously been demonstrated that DCs pulsed ex vivo with Toxoplasma gondii antigens trigger a systemic Th1-biased specific immune response and induce protective and specific antitoxoplasma immunity. In the present study, we demonstrate that tumor antigen-pulsed DCs matured in the presence of Toxoplasma gondii components induce a potent antitumor response in a mouse model of fibrosarcoma. Bone-marrow derived DCs (BMDCs) were cultured in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. After 5 days, tumor lysates with or without the T. gondii lysate were added to the culture for another 2 days. The cytokine production in the BMDC culture and the coculture supernatants of DCs and splenic cells was evaluated. For immunization, 7 days after tumor challenge, different groups of BALB/c mice received different kinds of DCs subcutaneously around the tumor site. Tumor growth was monitored, and 2 weeks after DC immunotherapy, the cytotoxic activity and the infiltration of CD8(+) T cells were monitored in different groups. According to the findings, immunotherapy with T. gondii-matured DCs led to a significant increase in the activity of cytotoxic T cells and decreased the rate of growth of the tumor in immunized animals. Immature DCs did not cause any change in cytotoxic activity or the tumor growth rate compared to that in the healthy controls. The current study suggests that a specific antitumor immune response can be induced by DCs matured with T. gondii components and provide the basis for the use of T. gondii in DC-targeted clinical therapies.

Background: The use of dendritic cells (DCs) as a cellular adjuvant provides a promising approach in immunotherapy of cancer. It has been demonstrated that Listeria monocytogenes activated DCs pulsed ex vivo with tumor antigens trigger a systemic Th1-biased specific immune response and a single dose of this vaccine will cause a considerable anti tumor immunity., Objective: The present study was designed to evaluate the ability of multiple doses of tumor antigen-pulsed DCs, matured in the presence of Listeria monocytogenes components in induction of a potent anti-tumor response and the prevention of tumor formation in an experimental model., Methods: Bone-marrow derived DCs (BMDCs) were cultured in the presence of GM-CSF and IL-4. After 5 days, tumor lysates with/without Listeria monocytogenes lysate were added to the culture media for another 2 days. Mice received mature and tumor antigen pulsed dendritic cells subcutaneously in 3 groups. Tumor growth was monitored and two weeks after immunotherapy, cytotoxic activity of CD8+ T cells was evaluated in different groups., Results: According to the findings, repeated doses of vaccine did not lead to a significant increase in the activity of cytotoxic T cells and decreased tumor growth of immunized animals., Conclusion: The current study suggests that increased doses of vaccine do not have sufficient efficiency for prevention of tumor induction. Generation of T regulatory responses upon repeated doses of such vaccines should be considered in future investigations.

Background: Bacterial DNA has immunostimulatory effects on different types of immune cells such as dendritic cells (DCs). Application of DCs as a cellular adjuvant represents a promising approach in the immunotherapy of infectious disease and cancers., Objective: To investigate the effect of tumor antigen pulsed DCs in the presence of CpG-1826 in treatment of a murine model of cancer., Methods: WEHI-164 cells (Balb/c derived fibrosarcoma cell line) were injected subcutaneously in the right flank of mice. Bone marrow cells were cultured in the presence of GM-CSF and IL-4. After 5 days, tumor lysate, CpG-1826, and oligodeoxynucleosides, as control, were added to the culture media and incubated for 2 days. Cytokine production in DCs culture media was measured by ELISA. Then DCs were injected subcutaneously around the tumor site in the right flank of mice. Tumor growth rate was monitored in case and control groups. Two weeks after DCs immunotherapy, cytotoxic assay was conducted using various amounts of effector (splenic T cells) and target cells (WEHI-164 or CT26) for 6 h., Results: Immunotherapy with DCs treated with CpG led to a significant increase in the activity of cytotoxic T cells and decreased tumor growth in immunized mice. In the control group which received DCs without CpG treatment, no change in cytotoxic activity and tumor growth rate was detected., Conclusion: The current study suggests that specific anti tumor immune responses can be induced by DCs matured with CpG and proposes CpG usage in DCs targeted clinical strategies.