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The induction of immunological tolerance is a promising strategy for managing autoimmune diseases, allergies, and transplant rejection. Tregitopes, a class of peptides, have emerged as potential agents for this purpose. They activate regulatory T cells, which are pivotal in reducing inflammation and promoting tolerance, by binding to MHC II molecules and facilitating their processing and presentation to Treg cells, thereby encouraging their proliferation. Moreover, Tregitopes influence the phenotype of antigen-presenting cells by attenuating the expression of CD80, CD86, and MHC class II while enhancing ILT3, resulting in the inhibition of NF-kappa B signaling pathways. Various techniques, including in vitro and in silico methods, are applied to identify Tregitope candidates. Currently, Tregitopes play a vital role in balancing immune activation and tolerance in clinical applications such as Pompe disease, diabetes-related antigens, and the prevention of spontaneous abortions in autoimmune diseases. Similarly, Tregitopes can induce antigen-specific regulatory T cells. Their anti-inflammatory effects are significant in conditions such as autoimmune encephalomyelitis, inflammatory bowel disease, and Guillain-Barré syndrome. Additionally, Tregitopes have been leveraged to enhance vaccine design and efficacy. Recent advancements in understanding the potential benefits and drawbacks of IVIG and the discovery of the function and mechanism of Tregitopes have introduced Tregitopes as a popular option for immune system modulation. It is expected that they will bring about a significant revolution in the management and treatment of autoimmune and immunological diseases. This article is a comprehensive review of Tregitopes, concluding with the potential of these epitopes as a therapeutic avenue for immunological disorders.
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Linfocitos T Reguladores , Humanos , Linfocitos T Reguladores/inmunología , Animales , Enfermedades del Sistema Inmune/inmunología , Enfermedades del Sistema Inmune/terapia , Tolerancia Inmunológica/inmunologíaRESUMEN
As an antibody-based therapy, plasma therapy has been used as an emergency therapeutic strategy against severe acute respiratory syndrome coronavirus type 2 infection. Due to the critical role of macrophages in coronavirus disease-19 (COVID-19)-associated hyperinflammation, the main objective of this study was to assess the effect of plasma transfusion on the expression levels of the inflammatory biomarkers involved in activation and pulmonary infiltration of macrophages. The target population included 50 severe hospitalized COVID-19 patients who were randomly assigned into 2 groups, including intervention and control. Serum levels of chemokine (C-C motif) ligand (CCL)-2, CCL-3, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. Moreover, quantitative real-time polymerase chain reaction (PCR) was carried out to assess the relative expression of nuclear factor (NF)-κB1, NF-κB2, nuclear factor erythroid 2 p45-related factor 2 (NRF-2), and thioredoxin-interacting protein genes. Sampling was done at baseline and 72 h after receiving plasma. The intervention group demonstrated significantly lower serum levels of IL-6, TNF-α, and CCL-3. In addition, real-time PCR data analyses showed that the relative expression of NF-κB2 was significantly declined in the patients who received plasma. The use of convalescent plasma probably has a significant inhibitory effect on the cytokines, chemokines, and inflammatory genes related to macrophage activation, which are closely associated with the worsening of clinical outcomes in severe COVID-19.
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Biomarcadores , Sueroterapia para COVID-19 , COVID-19 , Inmunización Pasiva , Macrófagos , SARS-CoV-2 , Humanos , COVID-19/terapia , COVID-19/sangre , COVID-19/inmunología , Masculino , Persona de Mediana Edad , Femenino , Biomarcadores/sangre , Macrófagos/inmunología , Macrófagos/metabolismo , SARS-CoV-2/inmunología , Adulto , Inflamación/sangre , Inflamación/terapia , Inflamación/inmunología , Anciano , Citocinas/sangre , Índice de Severidad de la EnfermedadRESUMEN
Scorpion venoms identified as agents with anti-tumor and anti-angiogenic features. Tumor microenvironment (TME) plays a pivotal role in the process of tumorigenesis, tumor development, and polarization of M2 phenotype tumor associated macrophages (TAMs). M2 polarized cells are associated with tumor growth, invasion, and metastasis. The fractionation process was performed by gel filtration chromatography on a Sephadex G50 column. To elucidate whether scorpion venom can alter macrophage polarization, we treated interleukin (IL)-4-polarized M2 cells with isolated fractions from Mesobuthus eupeus. Next, we evaluated the cytokine production and specific markers expression for M2 and M1 phenotype using enzyme linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR), respectively. The phagocytic capacity of macrophages was also assessed. In addition, the migration assay and MTT analysis were performed to investigate the effects of reprogrammed macrophages on the CT-26 colon cancer cells. The results indicated that F1 fraction of venom significantly upregulated the levels and expression of M1-associated cytokines and markers, including tumor necrosis factor-alpha (TNF-α) (p < 0.001), IL-1 (p < 0.01), interferon regulatory factor 5 (IRF5) (p < 0.0001), induced nitric oxide synthase (iNOS) (p < 0.0001), and CD86 (p < 0.0001), and downregulated M2-related markers, including transforming growth factor-beta (TGF-ß) (p < 0.05), IL-10 (p < 0.05), Fizz1 (p < 0.0001), arginase-1 (Arg-1) (p < 0.0001), and CD206 (p < 0.001). The macrophage phagocytic capacity was enhanced after treatment with F1 fraction (p < 0.01). Moreover, incubation of CT-26 cell line with conditioned media of F1-treated macrophages suppressed migration (p < 0.0001) and proliferation (p < 0.01) of tumor cells. In conclusion, our findings demonstrated the potential of Mesobuthus eupeus venom in M2-to-M1 macrophage polarization as a promising therapeutic approach against proliferation and metastasis of colon cancer cells.
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Animales Ponzoñosos , Citocinas , Venenos de Escorpión , Animales , Venenos de Escorpión/farmacología , Ratones , Línea Celular Tumoral , Citocinas/metabolismo , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Neoplasias del Colon/inmunología , Antineoplásicos/farmacología , Escorpiones , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Movimiento Celular/efectos de los fármacos , Fagocitosis/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacos , Activación de Macrófagos/efectos de los fármacos , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/efectos de los fármacos , Macrófagos Asociados a Tumores/metabolismo , Ratones Endogámicos BALB C , Células RAW 264.7 , Humanos , FenotipoRESUMEN
The tumor microenvironment (TME) with vital role in cancer progression is composed of various cells such as endothelial cells, immune cells, and mesenchymal stem cells. In particular, innate immune cells such as macrophages, dendritic cells, myeloid-derived suppressor cells, neutrophils, innate lymphoid cells, γδT lymphocytes, and natural killer cells can either promote or suppress tumor progression when present in the TME. An increase in research on the cross-talk between the TME and innate immune cells will lead to new approaches for anti-tumoral therapeutic interventions. This review primarily focuses on the biology of innate immune cells and their main functions in the TME. In addition, it summarizes several innate immune-based immunotherapies that are currently tested in clinical trials.
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Background : Colorectal cancer, a solid tumor with a high prevalence, contributes significantly to annual mortality rates. Various factors, including blood groups, may influence cancer risk. Multiple studies have suggested a potential connection between ABO and Rh blood groups and colorectal cancer risk. This study aims to investigate the role of ABO and Rh blood groups as risk factors in colorectal cancer patients. Materials and Methods: We conducted a retrospective study involving 71 colorectal cancer patients diagnosed between 2018 and 2020 in Khuzestan province, Iran, with known ABO blood types. Large-scale data from 29,922 blood donors in Khuzestan served as the healthy population control. The study analyzed the distribution of ABO blood groups among the blood donors. Results : Our findings revealed that the distribution of blood groups among colorectal cancer patients was as follows: O (31.0%), A (29.6%), B (29.6%), and AB (9.8%). However, our analysis did not establish a significant association between colorectal cancer risk and ABO antigens (P-value = 0.636) or Rh blood group (P = 0.198). Additionally, no significant differences in ABO blood types were observed concerning gender (P = 0.802), cancer type (P = 0.338), or tumor type (P = 0.207) among colorectal cancer patients. Conclusion : This study does not support a significant correlation between ABO and Rh blood groups and the risk of colorectal cancer, nor does it find associations with cancer type or tumor type.
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Two-dimensional (2D) van der Waals heterostructures outperform conventional anode materials for postlithium-ion batteries in terms of mechanical, thermal, and electrochemical properties. This study systemically investigates the performance of bilayer and trilayer C3N/blue phosphorene (C3N/BlueP) heterostructures as anode materials for potassium-ion batteries (KIBs) using first-principles density functional theory calculations. This study reveals that the adsorption and diffusion of K ions on bilayer and trilayer C3N/BlueP heterostructures are markedly superior to those of their monolayer counterparts. A bilayer heterostructure (C3N/BlueP) effectively reduces the bandgap of the BlueP monolayer (1.98 eV) to 0.02 eV, whereas trilayer heterostructures (bilayer-C3N/BlueP and C3N/bilayer-BlueP) exhibit metallic behavior with no bandgap. Additionally, the theoretical capacity of the bilayer and trilayer heterostructures ranges from 636.7 to 755.5 mA h g-1, considerably higher than the theoretical capacity of other prospective 2D heterostructures for KIBs investigated in the literature. This study also shows that the heterostructures exhibit K-ion diffusion barriers as low as 0.042 eV, ensuring the relatively fast diffusion of K ions.
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Background: Breast cancer and cervix cancer are the prevalent and deadly types of solid tumors around the world. According to the importance of cancer, it is necessary to understand predisposing factors that affect cancer risk. In this regard, previous studies suggest that blood types particularly ABO and Rh-Hr Blood-Group System could play roles in the risk and different features of cancers. In the present study, we aimed to evaluate the potential of ABO and Rh blood groups as risk factors for breast cancer and cervix cancer. Materials and Methods: A retrospective study included 109 and 14 patients diagnosed with breast cancer and cervix cancer, respectively with known ABO and Rh blood types, between 2018 and 2020 in Khuzestan province, Iran. For compression of ABO blood groups distribution between the cancer patients group and the healthy population, we used data from a large-scale study that report the distribution of ABO blood groups in 29,922 blood donors in Khuzestan province. Results: Based on obtained results the most frequent blood group is O followed by B, A, and AB in breast cancer and followed by A, B, and AB in cervix cancer. Results showed no significant association between ABO and Rh and the risk of breast and cervix cancer. Moreover, there is no relationship between blood types and clinic pathological features of breast cancer. Conclusion: Based on our data, ABO and in this regard, previous studies suggest that blood types particularly ABO and Rh-Hr Blood-Group System could play roles in the risk and different features of cancers. In the present study, we aimed to evaluate the potential of ABO and Rh blood groups as risk factors for breast cancer and cervix cancer do have not any association with the risk of breast and cervix cancer and their characteristics.
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BACKGROUND AND AIM: The hyperactive nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key factor for cytokine storm, chronic inflammation, and mortality in infected patients. On the subject of the regulation of the NLRP3-inflammasome activation, micro-ribonucleic acid (RNA)-223 (miR-223), among the major RNA molecules, has been thus far investigated in some inflammatory diseases along with interleukin-1 beta (IL-1ß) and NLRP3. Against this background, the present study aimed to compare healthy individuals and patients with severe COVID-19 with reference to the alterations in the expression of the miR-223, NLRP3, and IL-1ß axis and the serum IL-1ß levels. METHODS: In total, 40 patients with severe COVID-19, admitted to the Infectious Ward of Razi Hospital, Ahvaz, Iran, who were homogenous in terms of age (40 years old) and gender, were selected based on the inclusion and exclusion criteria. The real-time polymerase chain reaction (RT-PCR) technique was then applied to assess the expression of the miR-223, NLRP3, and IL-1ß genes, and enzyme-linked immunosorbent assay (ELISA) was then utilized to evaluate the serum IL-1ß levels, using patients' blood samples. Moreover, inflammatory biochemical markers of the participants were collected and recorded RESULTS: According to the study results, the IL-1ß expression was 3.9 times higher in the patients with COVID-19, compared with the control group (p = 0.0005). The NLRP3 expression was also 6.04 times greater in the infected patients, compared with the healthy individuals (p < 0.0001). On the other hand, the miR-223 expression was 5.37 times lower in the case group, compared with the controls (p = 0.04). CONCLUSION: The study findings indicated the potential role of miR-223 and the dysregulation of NLRP3 inflammasome followed by IL-1ß, as a regulatory factor in the pathogenesis of COVID-19, like that in other inflammatory diseases.
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COVID-19 , MicroARNs , Humanos , Adulto , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , SARS-CoV-2/genética , MicroARNs/genéticaRESUMEN
Background: Exosomes are nanoscale vesicles widely used as drug delivery systems. Mesenchymal stem cell (MSC)-derived exosomes have shown immunomodulatory potential. This study optimized loading OVA into the mice adipose tissue-derived MSC-isolated exosomes to prepare the OVA-MSC-exosome complex for allergen-specific immunotherapy. Methods: MSCs were harvested from mice adipose tissue and characterized by flow cytometry and evaluating differentiation potential. The exosomes were isolated and characterized via Dynamic Light Scattering, Scanning Electron Microscopy, and flow cytometry. Different concentrations of ovalbumin were incubated with MSC-exosome in various durations to optimize a more suitable protocol. BCA and HPLC analysis were used to quantify, and DLS was applied to qualify the prepared formulation of the OVA-exosome complex. Results: The harvested MSCs and isolated exosomes were characterized. Analysis of the OVA-exosome complex revealed that OVA in primary 500 µg/ml concentration and incubation for 6 h results in higher efficacy. Conclusions: Loading OVA into MSC-derived exosomes was successfully optimized and could be administrated for allergen-specific immunotherapy in the animal model.
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BACKGROUND: Allergen-specific sublingual immunotherapy (SLIT) was considered an interesting needle-free alternative for subcutaneous immunotherapy (SCIT). Mesenchymal stem cell (MSC)-derived exosomes were introduced as potent nanoscale delivery systems with immunomodulatory potentials. The current study investigated the therapeutic efficacy of SLIT using ovalbumin (OVA)-enriched MSC-derived exosomes formulation in a murine model of allergic asthma. MATERIAL AND METHODS: MSCs were harvested from mice adipose tissues. Then, exosomes were isolated, and OVA-loaded exosomes were prepared. Following sensitization, Balb/c mice received therapeutic formulation (10 µg/dose OVA-containing MSC-derived exosomes) twice a week for two months. Serum OVA-specific IgE levels as well as IFN-γ, IL-4, and TGF-ß secretions by cultured splenocytes were measured by ELISA. Also, lung tissue underwent histopathologic analysis, and the numbers of inflammatory cells and eosinophils in nasopharyngeal lavage fluid (NALF) were examined. RESULTS: SLIT using OVA-enriched exosomes significantly reduced IgE levels and IL-4 production, while the secretion of IFN-γ and TGF-ß were significantly elevated. Also, a decrease was observed in the numbers of total cells and eosinophils in the NALF, and lower levels of perivascular and peribronchiolar inflammation and cellular infiltrations were observed in the lung tissue. CONCLUSION: SLIT using OVA-loaded exosomes improved immunomodulatory responses and efficiently alleviated allergic inflammation.
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Exosomas , Células Madre Mesenquimatosas , Inmunoterapia Sublingual , Animales , Ratones , Alérgenos , Interleucina-4 , Inmunoglobulina E , Factor de Crecimiento Transformador beta , Inmunidad , Inflamación , Ratones Endogámicos BALB C , Ovalbúmina , Modelos Animales de Enfermedad , CitocinasRESUMEN
Depression is the most prevalent psychiatric disorder and has received more attention due to its adverse outcomes, including suicide and a severe decrease in social and individual functioning. To this end, the present study examined the effect of movement therapy and progressive muscle relaxation on the depression rate in depressed patients. In the present interventional study, 60 patients diagnosed with major depression and hospitalized at Moradi Hospital's psychiatric ward in Rafsanjan in 2020, with an age of at least 20 years, were randomly divided into two groups: the intervention group and the control group. The subjects in the intervention group attended 30 sessions of 30-45 mins, with the researcher performing a movement therapy program followed by 15 to 20 minutes of progressive muscle relaxation. The Beck Depression Inventory was used to measure the degree of depression along with clinical pre-and post-intervention interviews. The mean depression scores were 37.26±7.70 and 36.93±8.166 for the participants in the intervention group and control group before the intervention, indicating no statistically significant intergroup difference (P=0.871). The mean depression scores after the intervention for the subjects in the intervention group and control group were 8.01±5.22 and 22.96±9.43, respectively. The results showed a statistically significant difference between the groups (P=0.001), with a greater decrease in depression scores in the intervention group compared to the control group. According to the present research, movement therapy and progressive muscle relaxation interventions effectively reduced depression in patients.
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Entrenamiento Autogénico , Servicio de Psiquiatría en Hospital , Humanos , Adulto Joven , Adulto , Depresión , Escolaridad , HospitalesRESUMEN
BACKGROUND & OBJECTIVES: Tumor cells have various effects and dominance over other healthy cells. Cancer cells alter the cell program in healthy cells by secreting exosomes containing microRNAs involved in epithelial-mesenchymal transition (EMT). They can migrate to distant organs and establish a pre-metastatic niche. The purpose of this study was to determine the expression of miRNA-21-5p and miRNA-10b-5p, both of which are involved in EMT, in breast cancer-derived exosomes of various grades in order to identify new biomarkers involved in breast cancer progression. METHODS: In this study, a blood sample was taken from 60 patients with grades I, II, or III breast cancer, as well as twenty healthy individuals as a control group. The exosomes were then purified from serum samples, and their relative expression of miRNA-21-5p and miRNA-10b-5p was determined using the real-time PCR method. RESULTS: miRNA-21-5p expression was significantly increased in patients with breast cancer grades I, II, and III compared to the control group (p < 0.01), (p < 0.0001) and (p < 0.0001), respectively, as was miRNA-10b-5p expression in patients with breast cancer grades I, II, and III compared to the control group (p < 0.0001), (p < 0.0001) and (p < 0.0001), respectively. CONCLUSION: Our results show that both microRNAs increase as cells lose their differentiation and become more invasive, which is evidence of cancer progression. Hence, both microRNAs may have the potential to be used alone or in combination with other biomarkers for the diagnosis and prognosis of breast cancer.
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Neoplasias de la Mama , Exosomas , MicroARNs , Neoplasias de la Mama/sangre , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Transición Epitelial-Mesenquimal , Exosomas/genética , Exosomas/metabolismo , Femenino , Humanos , MicroARNs/sangre , Clasificación del TumorRESUMEN
Designing biomaterials capable of biomimicking wound healing and skin regeneration has been receiving increasing attention recently. Some biopolymers behave similarly to the extracellular matrix (ECM), supporting biointerfacial adhesion and intrinsic cellular interactions. Polydopamine (PDA) is a natural bioadhesive and bioactive polymer that endows high chemical versatility, making it an exciting candidate for a wide range of biomedical applications. Moreover, biomaterials based on PDA and its derivatives have near-infrared (NIR) absorption, excellent biocompatibility, intrinsic antioxidative activity, antibacterial activity, and cell affinity. PDA can regulate cell behavior by controlling signal transduction pathways. It governs the focal adhesion behavior of cells at the biomaterials interface. These features make melanin-like PDA a fascinating biomaterial for wound healing and skin regeneration. This paper overviews PDA-based biomaterials' synthesis, properties, and interactions with biological entities. Furthermore, the utilization of PDA nano- and microstructures as a constituent of wound-dressing formulations is highlighted.
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Materiales Biocompatibles , Polímeros , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/uso terapéutico , Indoles/química , Indoles/farmacología , Polímeros/farmacología , Polímeros/uso terapéutico , Cicatrización de HeridasRESUMEN
Aim: This study aimed to investigate the effects of natural adjuvants (G2 and PC) to activate natural killer cells in colorectal cancer. Background: Natural killer (NK) cells are an element of the innate immune system that can recognize and kill cancer cells and provide hope for cancer therapy. One of the current methods in cancer immunotherapy is NK cell therapy. Immunotherapy with NK cells has been limited because of the low number and cytotoxicity level of NK cells. Natural adjuvants such as PC and G2 may stimulate the immune system. It seems that these adjuvants could increase cytotoxic NK cells. Methods: Twelve patients with colorectal cancer and six healthy individuals qualified for inclusion in this study. Peripheral blood mononuclear cells (PBMCs) from each patient with two distinctive concentrations (105and 5×104 cells/well) were treated with Interleukin2 (IL2), PC, and G2 adjuvant separately. The NK cell's surface markers, including CD16, CD56, and NKG2D, were evaluated by flow cytometry. The cytotoxicity effect of treated PBMCs as effector cells against NK sensitive cell line (K562) was assessed using the LDH assay method. Results: The results revealed a significant increase in the level of CD16+NKG2D+ NK cells in PBMCs treated with the G2 group compared with the control group in CRC PBMC (p<0.001) as well as the normal PBMC group (p < 0.01). In addition, the results indicated a significant increase in the level of CD56+NKG2D+ cells in the PBMC treated with PC (p < 0.05) and G2 (p < 0.001) groups compared with the PBMC group. The cytotoxicity result of PBMC from CRC patients in 10:1 ratio of the effector: target showed that the cells' cytotoxicity in the PBMCs treated with PC (p<0.01) and G2 (p<0.05) was significantly higher than the untreated PBMC. Conclusion: According to the result of this study, it can be stated that the PC and G2 adjuvants could be candidates for inducing cytotoxic natural killer cells.
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BACKGROUND: Peptide-based immunotherapy (PIT) was introduced as an attractive approach in allergen-specific immunotherapy (AIT). However, PIT clinical trials have shown variable results, and immune response to peptides is not precisely predictable. On the other hand, induction of antigen-specific tolerance may be augmented when allergens are combined with the regulatory T cell epitope (Tregitope). This study aimed to evaluate the therapeutic administration of a plasmid DNA encoding Tregitope and ovalbumin (OVA) immunodominant epitope in the murine model of allergy. METHODS: Following the induction of allergic rhinitis by ovalbumin, vaccinated group received three doses of recombinant plasmid containing Signal peptide-Tregitope-OVA T cell epitope. After the final OVA challenge, clinical symptoms, histopathological changes, OVA-specific IgE level, and cytokine secretion pattern of spleen cells were examined. RESULTS: Our data are showing that AIT with the recombinant DNA vaccine significantly suppressed airway inflammation; reduced eosinophilic infiltration in the nasal mucosa; decreased expression level of IL-4 and IL-17 in spleen cells, while IFN-γ, IL-10, and TGF-ß expression were increased. Moreover, OVA-specific IgE levels were also decreased. CONCLUSION: These results suggest that Tregitope-immunodominant T cell epitope fusion can act as a safe and effective approach in DNA-based allergen-specific immunotherapy.
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Hipersensibilidad , Epítopos Inmunodominantes , Alérgenos , Animales , Citocinas , Desensibilización Inmunológica , Modelos Animales de Enfermedad , Epítopos de Linfocito T , Epítopos Inmunodominantes/uso terapéutico , Inmunoglobulina E/genética , Ratones , Ratones Endogámicos BALB C , Ovalbúmina , Péptidos , Plásmidos/genéticaRESUMEN
The expected crash frequency is the long-term average crash count for a specific site. It is extensively used to systematically evaluate the crash risk associated with roadway elements. To estimate the expected crashes, the Empirical Bayesian (EB) approach is typically employed. The EB method is a computationally convenient approximation to the Full Bayesian (FB) method, which gained popularity due to its simple interpretation, computational efficiency, and the ability to account for the regression to the mean bias. However, the common EB method used in traffic safety analysis is only applicable when the traditional Negative Binomial (NB) model is used. The NB model, however, is not a suitable choice when data is highly dispersed, skewed, or has a large number of zero observations. The Negative Binomial-Lindley (NB-L) model is a mixture of the NB and Lindley distributions and has shown superior fit compared to the NB model, especially when the dataset is characterized by excess zero observations. Even though several studies have used the NB-L in developing crash prediction models, the application of the NB-L in other safety-related tasks (e.g., hot spot identification) is largely neglected. This study proposed a framework to develop the EB method for the NB-L model and subsequently estimate the expected crash values. A comparison between the EB and FB estimates was performed to validate the approximation framework in general. The results indicated that the proposed EB framework is able to estimate expected crashes with comparable precision to the FB estimate, but with much less computational cost. In addition, a site ranking analysis using the EB estimates was conducted to validate the proposed approximation method in safety studies. However, it should be noted that any other type of safety analysis that requires access to the expected crashes can benefit from the proposed EB method. This study concluded that the proposed EB framework can properly approximate the underlying FB approach and can reasonably be considered as an alternative to the traditional EB formula derived from the NB model. The results of this study can help to extend the application of the advanced predictive models beyond predicting crashes to other safety-related tasks, with no additional computational efforts.
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Accidentes de Tránsito , Planificación Ambiental , Accidentes de Tránsito/prevención & control , Teorema de Bayes , Humanos , Modelos Lineales , Modelos Estadísticos , SeguridadRESUMEN
BACKGROUND: Tranilast is a potential NLRP3 inflammasome inhibitor that may relieve progressive inflammation due to COVID-19. AIM OF THE STUDY: To evaluate the therapeutic effects of Tranilast in combination with antiviral drugs in non-ICU-admitted hospitalized patients with COVID-19. METHODS: This study was an open-label clinical trial that included 72 hospitals admitted patients with severe COVID-19 at Razi Hospital, Ahvaz, Iran, from July 2020-August 2020. These patients were randomly assigned in a 1:1 ratio to control (30) and intervention groups (30). Patients in the control group received antiviral therapy, while patients in the intervention group received Tranilast (300 mg daily) in addition to the antiviral drugs for Seven days. The collected data, including the expression of inflammatory cytokine, laboratory tests, and clinical findings, was used for intragroup comparisons. RESULTS: The intervention group showed significantly lower levels of NLR (p = 0.001), q-CRP (p = 0.002), IL-1 (p = 0.001), TNF (p = 0.001), and LDH (p = 0.046) in comparison with the control group. The effect of intervention was significant in increasing the o2 saturation (F = 7.72, p = 0.007). Long hospitalization (four days or above) was 36.6% in the Tranilast and 66.6% in the control group (RR = 0.58; 95% CI: 0.38-1.06, p = 0.045). In the Tranilst and control groups, one and four deaths or hospitalization in ICU were observed respectively (RR = 0.31; 95% CI: 0.03-2.88, p = 0.20). CONCLUSIONS: Tranilast might be used as an effective and safe adjuvant therapy and enhance the antiviral therapy's efficacy for managing patients with COVID-19.
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Tratamiento Farmacológico de COVID-19 , Antivirales/uso terapéutico , Humanos , SARS-CoV-2 , Resultado del Tratamiento , ortoaminobenzoatosRESUMEN
Architecting an appropriate platform for biomedical applications requires setting a balance between simplicity and complexity. Polysaccharides (PSAs) play essential roles in our life in food resources, structural materials, and energy storage capacitors. Moreover, the diversity and abundance of PSAs have made them an indispensable part of food ingredients and cosmetics. PSA-based hydrogels have been extensively reviewed in biomedical applications. These hydrogels can be designed in different forms to show optimum performance. For instance, electroactive PSA-based hydrogels respond under an electric stimulus. Such performance can be served in stimulus drug release and determining cell fate. This review classifies and discusses the structure, properties, and applications of the most important polysaccharide-based electroactive hydrogels (agarose, alginate, chitosan, cellulose, and dextran) in medicine, focusing on their usage in tissue engineering, flexible electronics, and drug delivery applications.
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Materiales Biocompatibles/química , Sistemas de Liberación de Medicamentos , Hidrogeles/química , Polisacáridos/química , Ingeniería de Tejidos , Animales , Conductividad Eléctrica , HumanosRESUMEN
The present study conducted a placebo-controlled clinical trial to evaluate the impact of nano-curcumin on the inflammatory cytokines in mild-to-moderate hospitalized COVID-19 patients. A total of 60 COVID-19 patients were randomly divided into nano-curcumin and control groups, and then they received 240 mg/day nano-curcumin for 7 days. The clinical manifestation and laboratory parameters in patients were recorded on days 0 and seven. Also, SYBR Green real-time PCR and ELISA techniques were implicated in assessing the mRNA expression of IFN-γ, IL-1ß, IL-6, MCP-1, and TNF-α and the serum levels of IL-1ß, IL-6, and TNF-α inflammatory mediators, respectively. Although the clinical manifestations and laboratory parameters improved via the nano-curcumin treatment, the mRNA expression of IFN-γ (p = 0.006) and TNF-α (p = 0.04) were significantly reduced. Besides, a considerable difference was observed between the nano-curcumin and control groups in the expression of IFN-γ (p = 0.001), IL-1ß (p = 0.0002), and IL-6 (p = 0.008). In addition, there was a significant difference between the nano-curcumin and control groups in the serum levels of IL-1ß (p = 0.042). The evidence demonstrated that nano-curcumin could be implicated as a complementary medication to act as an antiinflammatory agent and inhibit inflammatory complications.
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Antiinflamatorios , COVID-19 , Curcumina , Antiinflamatorios/uso terapéutico , Curcumina/uso terapéutico , Citocinas , Humanos , SARS-CoV-2RESUMEN
In this study, the therapeutic efficacy of quercetin in combination with remdesivir and favipiravir, were evaluated in severe hospitalized COVID-19 patients. Our main objective was to assess the ability of quercetin for preventing the progression of the disease into critical phase, and reducing the levels of inflammatory markers related to SARS-Cov-2 pathogenesis. Through an open-label clinical trial, 60 severe cases were randomly divided into control and intervention groups. During a 7-day period, patients in the control group received antivirals, i.e., remdesivir or favipiravir, while the intervention group was treated with 1000 mg of quercetin daily in addition to the antiviral drugs. According to the results, taking quercetin was significantly associated with partial earlier discharge and reduced serum levels of ALP, q-CRP, and LDH in the intervention group. Furthermore, although the values were in normal range, the statistical outputs showed significant increase in hemoglobin level and respiratory rate in patients who were taking quercetin. Based on our observations, quercetin is safe and effective in lowering the serum levels of ALP, q-CRP, and LDH as critical markers involved in COVID-19 severity. However, according to the non-significant borderline results in comparing the mortality, the ICU-admission rate, and the duration of ICU-admission, further studies can be helpful to compensate the limitations of our study and clarify the therapeutic potential of quercetin in COVID-19 treatments.