Immunological Response against Breast Lineage Cells Transfected with Human Papillomavirus (HPV).

Breast cancer is the most common neoplasm worldwide. Viral infections are involved with carcinogenesis, especially those caused by oncogenic Human Papillomavirus (HPV) genotypes. Despite the detection of HPV in breast carcinomas, the virus's activity against this type of cancer remains controversial. HPV infection promotes remodeling of the host's immune response, resulting in an immunosuppressive profile. This study assessed the individual role of HPV oncogenes in the cell line MDA-MB-231 transfected with the E5, E6, and E7 oncogenes and co-cultured with peripheral blood mononuclear cells. Immunophenotyping was conducted to evaluate immune system modulation. There was an increase in CD4+ T cell numbers when compared with non-transfected and transfected MDA-MB-231, especially in the Treg profile. Pro-inflammatory intracellular cytokines, such as IFN-γ, TNF-α, and IL-17, were impaired by transfected cells, and a decrease in the cytolytic activity of the CD8+ and CD56+ lymphocytes was observed in the presence of HPV oncogenes, mainly with E6 and E7. The E6 and E7 oncogenes decrease monocyte expression, activating the expected M1 profile. In the monocytes found, a pro-inflammatory role was observed according to the cytokines released in the supernatant. In conclusion, the MDA-MB-231 cell lineage transfected with HPV oncogenes can downregulate the number and function of lymphocytes and monocytes.

Evaluation of antioxidant, immunomodulatory, and cytotoxic action of fractions from Eugenia uniflora L. and Eugenia malaccensis L.: correlation with polyphenol and flavanoid content.

An increasing number of biological activities presented by medicinal plants has been investigated over the years, and they are used in the search for new substances with lower side effects. Eugenia uniflora L. and Eugenia malaccensis L. (Myrtaceae) have many folk uses in various countries. This current study was designed to quantify the polyphenols and flavonoids contents and evaluate the immunomodulatory, antioxidant, and cytotoxic potentials of fractions from E. uniflora L. and E. malaccensis L. It was observed that the polyphenol content was higher in ethyl acetate fractions. These fractions have high antioxidant potential. E. malaccensis L. seeds showed the largest DPPH radical scavenger capacity (EC50 = 22.62). The fractions of E. malaccensis L. leaves showed lower antioxidant capacity. The samples did not alter the profile of proinflammatory cytokines and nitric oxide release. The results indicate that species of the family Myrtaceae are rich in compounds with antioxidant capacity, which can help reduce the inflammatory response.

Whole Yeast Vaccine Displaying ZIKV B and T Cell Epitopes Induces Cellular Immune Responses in the Murine Model.

Improving antigen presentation is crucial for the success of immunization strategies. Yeasts are classically used as biofactories to produce recombinant proteins and are efficient vehicles for antigen delivery, in addition to their adjuvant properties. Despite the absence of epidemic outbreaks, several vaccine approaches continue to be developed for Zika virus infection. The development of these prophylactic strategies is fundamental given the severity of clinical manifestations, mainly due to viral neurotropism. The present study aimed to evaluate in vivo the immune response induced by P. pastoris recombinant strains displaying epitopes of the envelope (ENV) and NS1 ZIKV proteins. Intramuscular immunization with heat-attenuated yeast enhanced the secretion of IL-6, TNF-α, and IFN-γ, in addition to the activation of CD4+ and CD8+ T cells, in BALB/c mice. P. pastoris displaying ENV epitopes induced a more robust immune response, increasing immunoglobulin production, especially IgG isotypes. Both proposed vaccines showed the potential to induce immune responses without adverse effects, confirming the safety of administering P. pastoris as a vaccine vehicle. Here, we demonstrated, for the first time, the evaluation of a vaccine against ZIKV based on a multiepitope construct using yeast as a delivery system and reinforcing the applicability of P. pastoris as a whole-cell vaccine.

Pectin-like polysaccharide extracted from leaves Crataeva tapia promotes antioxidant, immunomodulatory and emulsifiers applied in therapeutic formulations.

The objective of this work was to isolate a polysaccharide similar to pectin from Crataeva tapia leaves, not yet reported in the literature, and to evaluate its antioxidant, cytotoxic and immunomodulatory profile. Pectin was extracted from the leaves in three stages, organic solvent followed by acidified water and ethanol precipitation. With the pectin obtained, the physicochemical characterization of the molecule was carried out using high-performance liquid chromatography, Fourier-transform infrared spectroscopy, nuclear magnetic resonance (13C and 1H) and different thermal and elemental analysis. Furthermore, the antioxidant activities were evaluated in vitro, and using human peripheral blood mononuclear cell culture, cytotoxicity and immunostimulatory actions were investigated. Physical and chemical analyses showed characteristic signs of pectin. Antioxidant activity tests showed that pectin had moderate to low antioxidant activity. Furthermore, pectin did not affect the viability of erythrocytes and PBMC and induced an immunostimulatory state when it promoted the production of cytokines IL-6, IL-10 and TNF-α and increased the activation of CD8 + T lymphocytes. This study showed that pectin from Crataeva tapia is not cytotoxic and promoted a pro-inflammatory profile in peripheral blood mononuclear cell with application as an immunostimulating and emulsifying compound.

New imidazolidine derivatives as anti-Trypanosoma cruzi agents: structure-activity relationships.

Imidazolidine derivatives are key components for the development of bioactive compounds for the treatment of many diseases, especially Chagas. In fact, others studies showed that the imidazolidine-2,4-dione has stood out by presenting a wide spectrum of pharmacological activities including anticonvulsants, antiarrhythmic, and antiparasitic. In the present study, we investigated the morphological alterations induced by imidazolidine derivates LPSF/NN-52 and LPSF/NN-100 on trypomastigotes forms of Trypanosoma cruzi through ultrastructural analysis by electron microscopy. Many concentrations were used to measure the antiparasitic propriety promoted by imidazolidine derivatives, and our study indicates that parasites treated with 13 µg mL(-1) of the imidazolidine derivates for 24 h revealed severe damage to the parasite's mitochondrial complex. Beyond that, also observed in treated parasites were the following: myelin bodies, enlargement of cytoplasm vacuole, fragmentation of endoplasmic reticulum, and some treated samples clearly showed signs of necrosis. To confirm the ultrastructural results, some assays were performed for knowledge cellular death induction promoted by imidazolidine derivates against immune spleen cells. The induction of the necrotic process through derivatives LPSF/NN-52 and LPSF/NN-100 showed similar results in relation to nifurtimox and benznidazole. In the last assays, it was demonstrated that NN-100 was efficient against epimastigotes and trypomastigotes forms and these results reinforce the mechanisms of action of both new imidazolidine derivatives against T. cruzi.

Third-Generation Vaccines: Features of Nucleic Acid Vaccines and Strategies to Improve Their Efficiency.

Gene immunization comprises mRNA and DNA vaccines, which stand out due to their simple design, maintenance, and high efficacy. Several studies indicate promising results in preclinical and clinical trials regarding immunization against ebola, human immunodeficiency virus (HIV), influenza, and human papillomavirus (HPV). The efficiency of nucleic acid vaccines has been highlighted in the fight against COVID-19 with unprecedented approval of their use in humans. However, their low intrinsic immunogenicity points to the need to use strategies capable of overcoming this characteristic and increasing the efficiency of vaccine campaigns. These strategies include the improvement of the epitopes' presentation to the system via MHC, the evaluation of immunodominant epitopes with high coverage against emerging viral subtypes, the use of adjuvants that enhance immunogenicity, and the increase in the efficiency of vaccine transfection. In this review, we provide updates regarding some characteristics, construction, and improvement of such vaccines, especially about the production of synthetic multi-epitope genes, widely employed in the current gene-based vaccines.

Immunostimulatory activity of ConBr: a focus on splenocyte proliferation and proliferative cytokine secretion.

Lectins constitute a class of glycoproteins, which are capable of selectively and reversibly binding to carbohydrates, distinguishing small structural differences in complex oligosaccharides. Studies have shown that the binding of lectins to cell-surface carbohydrates can lead to various effects such as cellular proliferation, histamine release and cytokine production. Canavalia brasiliensis lectin (ConBr) is a (D-mannose) D-glucose lectin. In this study, murine splenocytes were cultured to determine the effect of ConBr on cell proliferation, nitric oxide (NO) release and cytokine secretion. In addition, cellular viability assays were performed to evaluate any mitogenic activity induced by this lectin. ConBr significantly increased cell proliferation with minimal cell damage. This lectin was able to induce an increased production of cytokines such as IL-2, IL-6 and IFN-γ and a decreased production of IL- 10. The release of NO was also observed. The results of this study indicate that ConBr could potentially be used as an immunomodulator.

Antischistosomal action of thioxo-imidazolidine compounds: an ultrastructural and cytotoxicity study.

Schistosomiasis is a disease caused by helminthes of the genus Schistosoma, which threatens approximately 207 million people worldwide. Recently, strains of Schistosoma mansoni appear to be developing tolerance and resistance against Praziquantel, the most commonly available drug on the market used in the treatment of disease. This worrisome development justifies studies that seek alternatives for the prevention, treatment and cure of this disease. This study aimed to evaluate the in vitro activity of new imidazolidine compounds 1-benzyl-4-[(4-chloro-phenyl)-hydrazono]-5-thioxo-imidazolidin-2-one (LPSF/PT-5) and 1-(4-chloro-benzyl)-4-[(4-fluoro-phenyl)-hydrazono]-5-thioxo-imidazolidin-2-one (LPSF/PT-11) against adult worms of S. mansoni. LPSF/PT-5 and LPSF/PT-11 imidazolidine derivatives showed relevant schistosomicidal activity in vitro and induced significant ultrastructural alterations in worms and cell death: results similar to praziquantel. Thus, it is possible that these imidazolidine derivatives can be future candidates as schistosomotic drugs, but further studies are needed to elucidate the induced mechanisms behind this response.

Development of synthetic antigen vaccines for COVID-19.

The current pandemic called COVID-19 caused by the SARS-CoV-2 virus brought the need for the search for fast alternatives to both control and fight the SARS-CoV-2 infection. Therefore, a race for a vaccine against COVID-19 took place, and some vaccines have been approved for emergency use in several countries in a record time. Ongoing prophylactic research has sought faster, safer, and precise alternatives by redirecting knowledge of other vaccines, and/or the development of new strategies using available tools, mainly in the areas of genomics and bioinformatics. The current review highlights the development of synthetic antigen vaccines, focusing on the usage of bioinformatics tools for the selection and construction of antigens on the different vaccine constructions under development, as well as strategies to optimize vaccines for COVID-19.

Characterization of a lignin from Crataeva tapia leaves and potential applications in medicinal and cosmetic formulations.

Lignins are phenolic macromolecules that have several applications. In this work, we examine some biological activities of a lignin-like macromolecule isolated from the Crataeva tapia leaves, not yet studied to evaluate its potential applications in medicinal and cosmetic formulations. Lignin was obtained by alkaline delignification and its physical-chemical characterization was made by means of FT-IR, UV-Vis, NMR spectroscopy, elementary analysis, molecular mass determination and thermal analysis. Lignin is of the GSH type, with levels of hydrogen (5.10%), oxygen (27.18%), carbon (67.60%), nitrogen (0.12%) and phenolic content of 189.6 ± 9.6 mg GAE/g. In addition, it is a thermally stable macromolecule with low antioxidant activity. Cytotoxicity and cytokine production were assessed by flow cytometry. The photoprotective activity was evaluated by adding different concentrations of lignin to a commercial cream. Lignin was not cytotoxic, it stimulated the production of TNF-α, IL-6 and IL-10 and did not promote a significant change in nitric oxide levels. In addition, this macromolecule was able to promote increased absorption of ultraviolet light from a commercial cream. These results reinforce the ethnopharmacological use of C. tapia leaves and suggest the need for further studies to determine the potential medicinal and cosmetic applications (sunscreen) of lignin from C. tapia leaves.

Evaluation of the In Vivo Acute Toxicity and In Vitro Hemolytic and Immunomodulatory Activities of the Moringa oleifera Flower Trypsin Inhibitor (MoFTI).

BACKGROUND: Protease inhibitors have been isolated from plants and present several biological activities, including immunomodulatory action. OBJECTIVE: This work aimed to evaluate a Moringa oleifera flower trypsin inhibitor (MoFTI) for acute toxicity in mice, hemolytic activity on mice erythrocytes and immunomodulatory effects on mice splenocytes. METHODS: The acute toxicity was evaluated using Swiss female mice that received a single dose of the vehicle control or MoFTI (300 mg/kg, i.p.). Behavioral alterations were observed 15-240 min after administration, and survival, weight gain, and water and food consumption were analyzed daily. Organ weights and hematological parameters were analyzed after 14 days. Hemolytic activity of MoFTI was tested using Swiss female mice erythrocytes. Splenocytes obtained from BALB/c mice were cultured in the absence or presence of MoFTI for the evaluation of cell viability and proliferation. Mitochondrial membrane potential (Δψm) and reactive oxygen species (ROS) levels were also determined. Furthermore, the culture supernatants were analyzed for the presence of cytokines and nitric oxide (NO). RESULTS: MoFTI did not cause death or any adverse effects on the mice except for abdominal contortions at 15-30 min after administration. MoFTI did not exhibit a significant hemolytic effect. In addition, MoFTI did not induce apoptosis or necrosis in splenocytes and had no effect on cell proliferation. Increases in cytosolic and mitochondrial ROS release, as well as Δψm reduction, were observed in MoFTI-treated cells. MoFTI was observed to induce TNF-α, IFN-γ, IL-6, IL-10, and NO release. CONCLUSION: These results contribute to the ongoing evaluation of the antitumor potential of MoFTI and its effects on other immunological targets.

Cramoll 1,4 lectin increases ROS production, calcium levels, and cytokine expression in treated spleen cells of rats.

This study reports the in vivo stimulatory effects of Cramoll 1,4 on rat spleen lymphocytes as evidenced by an increase in intracellular reactive oxygen species (ROS) production, Ca(2+) levels, and interleukin (IL)-1beta expression. Cramoll 1,4 extracted from seeds of the Leguminosae Cratylia mollis Mart., is a lectin with antitumor and lymphocyte mitogenic activities. Animals (Nine-week-old male albino Wistar rats, Rattus norvegicus) were treated with intraperitoneal injection of Cramoll 1,4 (235 microg ml(-1) single dose) and, 7 days later, spleen lymphocytes were isolated and analyzed for intracellular ROS, cytosolic Ca(2+), and IL-6, IL-10, and IL-1 mRNAs. Cell viability was investigated by annexin V-FITC and 7-amino-actinomycin D staining. The data showed that in lymphocytes activated by Cramoll 1,4 the increase in cytosolic and mitochondrial ROS was related to higher cytosolic Ca(2+) levels. Apoptosis and necrosis were not detected in statistically significant values and thus the lectin effector activities did not induce lymphocyte death. In vivo Cramoll 1,4 treatment led to a significant increase in IL-1beta but IL-6 and -10 levels did not change. Cramoll 1,4 had modulator activities on spleen lymphocytes and stimulated the Th2 response.

Biological and immunological activity of new imidazolidines against adult worms of Schistosoma mansoni.

The only drug available for treating schistosomiasis is praziquantel, however there are already reports of resistance to its use in treatment, making it necessary to search and develop new compounds to combat schistosomiasis. We tested, in vitro, two new products, Laboratório de Planejamento de Síntese de Fármacos (LPSF)/5-(4-chloro-benzylidene-3-(4-nitrebenzyl)-4-thioxo-imidazolidin-2-one (RZS-2) and LPSF/5-(4-fluoride-benzylidene-3-(4-nitrebenzyl)-4-thioxo-imidazolidin-2-one (RZS-5) imidazolidines, against adult worms of Schistosoma mansoni. Efficacy and safety of these compounds were analyzed through IC50 cytotoxicity, immune response and cell viability tests. At different concentrations ranging from 40-640 microM, the imidazolidines produced motor abnormalities, inhibition of pairing and oviposition and mortality within 24 h at the higher concentrations. Although not triggering changes in IFN-gamma and IL-10, LPSF/RZS-2 and LPSF/RZS-5 induced production of nitric oxide and showed similar behavior to praziquantel in the cell death test.

Immunomodulatory response of Cramoll 1,4 lectin on experimental lymphocytes.

Cramoll 1,4 is a lectin extracted from Cratylia mollis Mart. seeds that has shown antitumor and lymphocyte mitogenic activities in other studies. The aim of this work was to investigate, in vitro, the immunomodulatory activity of Cramoll 1,4 on experimental cultures of mice lymphocytes through cytotoxic assays, nitric oxide (NO) concentrations and IL-10 and IFN-γ production. Cramoll 1,4 did not show cytotoxic activity at 1-25 µg/mL concentrations, similar results were observed with concanavalin A (Con A) and phytohemagglutinin (PHA) lectins. The minimum production of IL-10 was observed in splenocytes cultivated with Con A, PHA and Cramoll 1,4 lectins. However, splenocytes treated with Cramoll 1,4 showed higher IFN-γ production in comparison with PHA and Con A (p < 0.05 for both). Production of NO was effectively suppressed in murine cells stimulated with the lectins and was only detected after 72 h for PHA in relation to non-stimulated lymphocytes (p < 0.05). Cramoll 1,4 was not toxic to murine lymphocytes, induced Th1 response through IFN-γ production and showed antiinflammatory activity through NO suppression. Therefore, Cramoll 1,4 can be considered a lectin with immunomodulatory activity.

Schinus terebinthifolia leaf lectin (SteLL) is an immunomodulatory agent by altering cytokine release by mice splenocytes.

Schinus terebinthifolia leaf lectin (SteLL) was reported to be an antimicrobial and antitumor agent. In this work, we evaluated the immunomodulatory activity of SteLL on mice splenocytes and also determined its native molecular mass and putative sequence similarities with plant proteins. The effects of SteLL (12.5 µg/mL) on viability, cytosolic Ca2+ concentration ([Ca2+]cyt), cytosolic and mitochondrial levels of reactive oxygen species (ROS), and mitochondrial transmembrane potential (ΔΨm) of mice splenocytes were determined. In addition, the culture supernatants were collected for quantification of interleukins (IL), tumor necrosis factor (TNF), interferon-gamma (IFN-γ) and nitric oxide (NO). SteLL showed a native molecular mass of 12.4 kDa and tandem mass spectrometry (MS/MS) ions search revealed similarities with adenosine triphosphate (ATP) synthase and F1-ATPase from plants (4% and 6% coverage, respectively). SteLL was not toxic to splenocytes, did not alter the [Ca2+]cyt and ROS levels, and slightly reduced ΔΨm. The presence of SteLL stimulated the cells to release pro-inflammatory cytokines (IL-17A, TNF-α, IFN-γ and IL-2) and also of IL-4, an anti-inflammatory cytokine that can prevent exacerbated inflammation. SteLL induced decrease in the secretion of NO. In conclusion, SteLL has biotechnological potential as an immunomodulator agent for use in studies employing cultures of immune cells. In addition, the anti-infectious and antitumor properties of the leaves may involve the immunomodulation property of SteLL.

Immunostimulatory and antioxidant activities of a lignin isolated from Conocarpus erectus leaves.

In this work, we investigated the antioxidant and immunomodulatory activities of a lignin isolated from Conocarpus erectus leaves. The lignin was characterized by FTIR, 1H NMR, 13C NMR and gel permeation chromatography analysis as well as ultraviolet/visible absorption spectra. The lignin was evaluated for total antioxidant activity (TAA), DPPH and ABTS+ scavenging abilities, and by a lipid peroxidation inhibition assay. Immunomodulatory activity of the lignin (10 µg/mL) on human peripheral blood mononuclear cells (PBMCs) was determined. The C. erectus lignin was found to be of the guaiacyl-syringyl-p-hydroxyphenyl (G-S-H) type, with an average molecular weight of 2709 Da (polydispersity index: 2.1). It showed low TAA (17.92%) and moderate antioxidant activity against DPPH and ABTS+ (IC50: 231.16 and 356.03 µg/mL, respectively). It also inhibited lipid peroxidation by 42.14%. The lignin promoted an increase in mitochondrial ROS levels as well as cytosolic Ca2+ in PBMCs. In addition, it promoted the differentiation and activation of CD8+ T lymphocytes, differentiation of CD14+ monocytes, and stimulated the release of nitric oxide and cytokines, mainly those linked to a Th1 response. The results showed that the C. erectus lignin may be used in future studies in which the modulation of the immune response is a key factor.

Lignin isolated from Caesalpinia pulcherrima leaves has antioxidant, antifungal and immunostimulatory activities.

Caesalpinia pulcherrima is a shrub with worldwide distribution used as an ornamental plant. In this study, we extracted a lignin from the C. pulcherrima leaves and investigated its biological functions. The lignin was characterized by FT-IR, UV-Vis, GPC, TGA and nuclear magnetic resonance (1H and 13C). The antioxidant activity was evaluated using phosphomolybdenum complexation methods (TAA), sequestration of DPPH and ABTS radicals, reducing power, formation of nitrite radical and iron chelating activity (Fe2 +). Antifungal activity was made using Candida spp., Aspergillus spp. and Cryptococcus neoformans strains. Cytotoxicity, oxidative stress, and cytokine production were performed using mouse splenocytes. The lignin showed maximal UV-Vis at ~280 nm, 22.27 L/g·cm of absorptivity and, 2,503 kDa of molecular weight. Phenolic compounds (41.33 ± 0.65 mg GAE/g) and indications of a guaiacyl-syringyl-hydroxyphenyl (GSH)-type composition were found. Antioxidant activities of lignin to TAA (40±1.2%) and to DPPH (16.9±0.2%) was high and showed antifungal potential, especially against Candida spp. (IC50 = 31.3 µg/mL) and C. neoformans (15.6 µg/mL). In mouse splenocytes, the lignin was not cytotoxic and stimulated the cell proliferation and cytokine release. These results indicate that C. pulcherrima lignin has the potential to be used as antifungal and immunostimulant compound.

Lignins isolated from Prickly pear cladodes of the species Opuntia fícus-indica (Linnaeus) Miller and Opuntia cochenillifera (Linnaeus) Miller induces mice splenocytes activation, proliferation and cytokines production.

Opuntia fícus-indica and Opuntia cochenillifera are species of Cactaceae, found in the arid regions of the planet. They present water, cellulose, hemicellulose, pectins, extractives, ashes and lignins. Here we aimed to study the immunomodulatory action of lignins from these two species against mice splenocytes, since no study for this purpose has yet been reported. The antioxidant activities of these lignins were evaluated by the DPPH, ABTS, NO assays and total antioxidant activity. Cytotoxicity was evaluated through Annexin V-FITC and propidium iodide-PE probs and cell proliferation was determined by CFSE. Immunomodulation studies with Opuntia lignins obtained were performed through investigation of ROS levels, cytosolic calcium release, changes on mitochondrial membrane potential, cytokine production and NO release. Results showed that Opuntia cochenillifera lignin presented more phenolic amount and antioxidant activities than Opuntia ficius-indica. Both lignins showed high cell viability (>96%) and cell proliferation. Activation signal was observed for both lignins with increase of ROS and cytosolic calcium levels, and changes in mitochondrial membrane potential. In addition, lignins induced high TNF-α, IL-6 and IL-10 production and reduced NO release. Therefore, these lignins present great potential to be used as molecules with a proinflammatory profile, being shown as a promising therapeutic agent.

Evaluation of antitumor activity and toxicity of Schinus terebinthifolia leaf extract and lectin (SteLL) in sarcoma 180-bearing mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Schinus terebinthifolia Raddi is a plant broadly used in folk medicine and the use of its leaf extract as an antitumor agent has been reported. AIM OF THE STUDY: To evaluate the antitumor potential and the toxicity of saline extract (SE) and lectin (SteLL) from S. terebinthifolia leaves in sarcoma 180-bearing mice. MATERIALS AND METHODS: Cytotoxicity to sarcoma 180 cells was tested in vitro, and antitumor assay was performed using Swiss female mice. The treatments (0.15 M NaCl, negative control; methotrexate 1.5 mg/kg, positive control; SE 100 mg/kg; SteLL 1 and 5 mg/kg) by intraperitoneal injections started on the 8th day after tumor inoculation and lasted 7 days. It was analyzed: tumor weight; number and gauge of tumor vessels; hematological and biochemical parameters; histopathological changes; and occurrence of micronuclei in bone marrow cells. RESULTS: SE and SteLL showed IC50 values (concentrations that reduced cell viability to 50%) of 301.65 and 8.30 µg/mL, respectively. The lectin was able to induce apoptosis. Treatments with the extract and lectin caused a 57.6-73.6% reduction in tumor weight, which was not significantly different from the reduction in the methotrexate group. Tumors of animals treated with SteLL at 5 mg/kg showed reduced number of secondary vessels while the gauge was lower in all treated groups. In the groups treated with SteLL, tumors showed reduced and slightly vascularized parenchyma, with necrosis in the center and at the periphery. No alterations in the blood levels of urea, creatine, and glucose were detected while serum AST level was moderately increased in the SE group. Histopathological analysis revealed vacuolization and steatosis in the liver of animals treated with the extract and lectin. In addition, the treatments with SE and SteLL resulted in the reduction of filtration space and alterations in tubular architecture in kidneys. In respect to hematological parameters, it was only detected increase in the number of monocytes in SE group. The extract and lectin did not induce the formation of micronuclei in the bone marrow cells. CONCLUSIONS: SE and SteLL had antitumor effect against sarcoma 180 without inducing hematological changes and genotoxic effects in mice; however, some degree of hepatic and renal toxicity was observed, suggesting the evaluation of drug delivery strategies in the future.

Viral Modulation of TLRs and Cytokines and the Related Immunotherapies for HPV-Associated Cancers.

The modulation of the host innate immune system is a well-established carcinogenesis feature of several tumors, including human papillomavirus- (HPV-) related cancers. This virus is able to interrupt the initial events of the immune response, including the expression of Toll-like receptors (TLRs), cytokines, and inflammation. Both TLRs and cytokines play a central role in HPV recognition, cell maturation and differentiation as well as immune signalling. Therefore, the imbalance of this sensitive control of the immune response is a key factor for developing immunotherapies, which strengthen the host immune system to accomplish an efficient defence against HPV and HPV-infected cells. Based on this, the review is aimed at exposing the HPV immune evasion mechanisms involving TLRs and cytokines and at discussing existing and potential immunotherapeutic TLR- and cytokine-related tools.