RESUMEN
N-Acetylcysteine (NAC) is a chemical compound with anti-inflammatory and antioxidant activity and acts as a free radical scavenger. Elaeagnus angustifolia (EA) is a plant native to the western part of Iran, with antioxidant and anti-inflammatory properties. The present study been taken evaluated the protective effect afforded by EA and NAC extracts on carrageenan-induced acute lung injury in Wistar rats. In this study, 42 rats were randomly assigned into seven groups. NAC and EA extracts were orally administered once/day for 21 continuous days. Pulmonary damage was induced by intratracheal injection of 100 µl of 2% λ-Carrageenan on day 21. Twenty-four hours post-surgery, the rats were euthanized and the samples were collected. Pretreatment with NAC and EA extracts reduced the total and differential cell accumulation as well as IL-6, and TNF-α cytokines. Antioxidant indicators demonstrate that in the groups receiving NAC and EA extract, MDA decreased while thiol and antioxidant capacity elevated. Treatment with NAC and EA significantly reduced Carrageenan-induced pathological pulmonary tissue injury. NAC and EA extract has protective effects on acute carrageenan-induced lung injury.
Asunto(s)
Lesión Pulmonar Aguda , Elaeagnaceae , Acetilcisteína/farmacología , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/patología , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Carragenina/farmacología , Citocinas , Elaeagnaceae/química , Depuradores de Radicales Libres/farmacología , Interleucina-6 , Pulmón , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Compuestos de Sulfhidrilo/farmacología , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
BACKGROUND: To examine the effects of BI 1029539 (GS-248), a novel selective human microsomal prostaglandin E synthase-1 (mPGES-1) inhibitor, in experimental models of acute lung injury (ALI) and sepsis in transgenic mice constitutively expressing the mPGES1 (Ptges) humanized allele. METHODS: Series 1: Lipopolysaccharide (LPS)-induced ALI. Mice were randomized to receive vehicle, BI 1029539, or celecoxib. Series 2: Cecal ligation and puncture-induced sepsis. Mice were randomized to receive vehicle or BI 1029539. RESULTS: Series 1: BI 1029539 or celecoxib reduced LPS-induced lung injury, with reduction in neutrophil influx, protein content, TNF-É, IL-1ß and PGE2 levels in bronchoalveolar lavage (BAL), myeloperoxidase activity, expression of mPGES-1, cyclooxygenase (COX)-2 and intracellular adhesion molecule in lung tissue compared with vehicle-treated mice. Notably, prostacyclin (PGI2) BAL concentration was only lowered in celecoxib-treated mice. Series 2: BI 1029539 significantly reduced sepsis-induced BAL inflammatory cell recruitment, lung injury score and lung expression of mPGES-1 and inducible nitric oxide synthase. Treatment with BI 1029539 also significantly prolonged survival of mice with severe sepsis. Anti-inflammatory and anti-migratory effect of BI 1029539 was confirmed in peripheral blood leukocytes from healthy volunteers. CONCLUSIONS: BI 1029539 ameliorates leukocyte infiltration and lung injury resulting from both endotoxin-induced and sepsis-induced lung injury.
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Lesión Pulmonar Aguda , Sepsis , Lesión Pulmonar Aguda/tratamiento farmacológico , Animales , Ciclooxigenasa 2/metabolismo , Dinoprostona , Modelos Animales de Enfermedad , Humanos , Pulmón/metabolismo , Ratones , Óxido Nítrico Sintasa de Tipo II , Prostaglandina-E Sintasas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Human dental pulp stem cells (hDPSCs) have significant potential of immunomodulatory for therapeutic and regenerative biomedical applications compared to other mesenchymal stem cells (MSCs). Nowadays, alteration of gene expression is an important way to improve the performance of MSCs in the clinic. MicroRNAs (miRs) and CD200 are known to modulate the immune system in MSCs. Curcumin is famous for its anti-inflammatory impacts. Phytosomal curcumin (PC) is a nanoparticle synthesized from curcumin that removes the drawbacks of curcumin. The purpose of this research was to assess the effects of PC on the expression of the CD200 and four key miRNAs in immune system. PC (30 µM) treatment of hDPSCs could ameliorate their immunoregulatory property, presented by reduced expressions of miR-21, miR-155 and miR-126, as well as enhanced expressions of miR-23 and CD200. The PC was also able to reduce PI3K\AKT1\NF-κB expressions that were target genes for these miRs and involved in inflammatory pathways. Moreover, PC was more effective than curcumin in improving the immune modulation of hDPSCs. Evidence in this study suggested that PC mediates immunoregulatory activities in hDPSC via miRs and CD200 to regulate PI3K\AKT1\NF-κB signalling pathways, which may provide a theoretical basis for PC in the treatment of many diseases. SIGNIFICANCE OF THE STUDY: Autoimmune diseases or tooth caries are partly attributed to global health problems and their common drug treatments have several side effects. The goal of this study is dentin regeneration and autoimmune diseases treatment via stem cell-based approaches with phytosomal curcumin (PC), for the first time. Because dental pulp stem cells have unique advantages (including higher immunomodulatory capacity) over other mesenchymal stem cells, we considered them the best option for treating these diseases. Using PC, we try to increase the immunomodulatory properties of these cells.
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Antígenos CD/genética , Curcumina/farmacología , Pulpa Dental/efectos de los fármacos , Inflamación/tratamiento farmacológico , MicroARNs/antagonistas & inhibidores , Células Madre/efectos de los fármacos , Antígenos CD/inmunología , Células Cultivadas , Curcumina/química , Pulpa Dental/inmunología , Humanos , Inflamación/inmunología , MicroARNs/genética , MicroARNs/inmunología , Nanopartículas/química , Células Madre/inmunologíaRESUMEN
Nasal polyps (NP) are associated with inflamed mucosa of unknown etiology. The role of T cells in nasal polyposis is unclear. Invariant natural killer T cells (iNKT) can promote Th2 responses and have been implicated in some types of asthma. As there are shared inflammatory pathways involved in asthma and NPs, we evaluated the frequency of iNKT in 17 patients with NPs, but without asthma. A median of 6% polyp cells were T lymphocytes, of which iNKT were 0 to 2.38% (mean 0.674%). In the matched group (nâ¯=â¯10), iNKT in NPs was significantly higher than PBMCs (1.057% vs 0.155%, Pâ¯<â¯0.05). Relative expression of Vα24 to TCR-beta genes in polyps (nâ¯=â¯14) was higher than blood in matched samples (nâ¯=â¯4). The presence of greater proportions of iNKT in NPs than in blood suggests that iNKT may play a role in the pathogenesis of nasal polyposis.
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Pólipos Nasales/patología , Células T Asesinas Naturales/patología , Adolescente , Adulto , Enfermedad Crónica , Femenino , Genes Codificadores de la Cadena beta de los Receptores de Linfocito T/genética , Humanos , Inmunoglobulina E/metabolismo , Recuento de Leucocitos , Leucocitos Mononucleares , Masculino , Persona de Mediana Edad , Pólipos Nasales/genética , Pólipos Nasales/metabolismo , Pólipos Nasales/cirugía , Receptores de Antígenos de Linfocitos T/genética , Rinitis/genética , Rinitis/metabolismo , Rinitis/patología , Sinusitis/genética , Sinusitis/metabolismo , Sinusitis/patología , Adulto JovenRESUMEN
OBJECTIVES: Smoking of water pipe (WP) and cigarettes has recently turned into a major global health burden. The present study aimed at assessing WP and cigarette smoking among Zahedan University of Medical Sciences (ZUMS) students in Iran. METHODS: A cross-sectional survey was conducted on 500 students in ZUMS (182 males, 318 females). The subjects were selected through randomized cluster sampling. Morgan's chart was applied to calculate the sample size; 96.6% of the attendees completed a questionnaire designed to address the aims of the study. RESULTS: The mean age of the subjects was 21.2 ± 2.4 years. WP and cigarette smoker rates were at 31.2% and 15.2%, respectively. The age of smoking initiation ranged between 15 and 20 years. Friends played crucial roles in triggering the smoking in both groups of WP and cigarette smokers (78% and 54%, respectively). The main reasons for WP and cigarette smoking were entertainment followed by curiosity. Furthermore, males used more cigarette (26.5 vs. 8.7%) and WP (50.6 vs. 20.4%) than females. Among father and mother smokers, respectively, 54.2% and 60% of children were also WP smokers (p = 0.001). Also, 21.9% and 60% of children smoking cigarettes had father and mother smokers, respectively (p = 0.05). CONCLUSION: Tobacco use, especially for WP seems to be at alarming rates among medical students in Iran. It is highly recommended to control the progressive prevalence of WP smoking by governmental/academic preventive measures as educational and smoking cessation activities.
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Fumar Cigarrillos , Estudiantes de Medicina , Fumar en Pipa de Agua , Adolescente , Niño , Estudios Transversales , Femenino , Humanos , Irán/epidemiología , Masculino , Prevalencia , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Kinin B1 receptors are implicated in asthmatic airway inflammation. Here we tested this hypothesis by examining the anti-inflammatory effects of BI113823, a novel non-peptide orally active kinin B1 receptor antagonist in mice sensitized to ovalbumin (OVA). Male Balb-c mice were randomly assigned to four study groups: (1) control, (2) OVA+vehicle, (3) OVA+BI113823, (4) OVA+dexamethasone. Mice were sensitized intraperitoneally with 75µg ovalbumin on days 1 and 8. On days 15-17, mice were challenged intranasally with 50µg of ovalbumin. Mice received vehicle, BI113823, or dexamethasone (positive control) on days 16-18. On day 19, bronchoalveolar lavage (BAL) and lung tissue were collected for biochemical and immuno-histological analysis. Compared to controls treatment with BI113823 significantly reduced the numbers of BAL eosinophils, macrophages, neutrophils and lymphocytes by 58.3%, 61.1%, 66.4% and 56.0%, respectively. Mice treated with dexamethasone showed similar reductions in BAL cells. Treatment with BI113823 and dexamethasone also significantly reduced total protein content, IgE, TNF-α and IL-1ß in lavage fluid, reduced myeloperoxidase activity, mucus secretion in lung tissues, and reduced the expression of B1 receptors, matrix metalloproteinase (MMP)-2 and cyclooxygenase (COX)-2 compared to vehicle-treated mice. Only BI113823 reduced MMP-9 and inducible nitric oxide synthase (iNOS). BI113823 effectively reduced OVA-induced inflammatory cell, mediator and signaling pathways equal to or greater than that seen with steroids in a mouse asthma model. BI113823 might be useful in modulating inflammation in asthma.
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Antiinflamatorios/uso terapéutico , Asma/tratamiento farmacológico , Antagonistas del Receptor de Bradiquinina B1/uso terapéutico , Alérgenos , Animales , Antiinflamatorios/farmacología , Asma/inmunología , Asma/metabolismo , Asma/patología , Antagonistas del Receptor de Bradiquinina B1/farmacología , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Recuento de Células , Ciclooxigenasa 2/inmunología , Dexametasona/farmacología , Inmunoglobulina E/inmunología , Interleucina-1beta/inmunología , Pulmón/metabolismo , Pulmón/patología , Masculino , Metaloproteinasa 2 de la Matriz/inmunología , Ratones Endogámicos BALB C , Moco/metabolismo , Ovalbúmina , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
OBJECTIVES: This study was undertaken to examine the effects of BI113823, a potent small molecule orally active nonpeptide B1 receptor antagonist, in an experimental model of endotoxin-induced direct lung injury in mice and indirect lung injury and survival in cecal ligation and puncture-induced polymicrobial sepsis in rats. DESIGN: Experimental, prospective study. SETTING: University research laboratory. SUBJECTS: Male BALB/c mice and male Wistar rats. INTERVENTIONS: Series 1: acute lung injury was induced in mice by intratracheal injection of lipopolysaccharide. Mice were then randomly assigned to receive treatment of vehicle, BI113823, or dexamethasone. Bronchoalveolar lavage fluid and lung tissues were analyzed for inflammatory cell influx and various histologic variables. Series 2: sepsis was induced by cecal ligation and puncture in anesthetized rats. Animals were then randomly assigned to receive treatment of vehicle or BI113823. Experiments were terminated at 20 hours and 7 days following cecal ligation and puncture, respectively. MEASUREMENTS AND MAIN RESULTS: Series 1: treatment with BI113823 significantly reduced lipopolysaccharide-induced neutrophil influx in bronchoalveolar lavage fluid. The BI113823 group had significantly lower lung vascular permeability, lung water content, myeloperoxidase activity, lung apoptosis and lung injury scores, total protein content, and tumor necrosis factor-α and interleukin-1ß levels compared with vehicle controls. In addition, nuclear factor-κB phosphorylation, nuclear translocation, and cyclooxygenase-2 and inducible nitric oxide synthase expression in the lung were attenuated in BI113823-treated animals compared with vehicle controls. Series 2: BI113823 significantly reduced sepsis-induced macrophage recruitment, protein content, and tumor necrosis factor-α and interleukin-1ß levels in lavage fluid and also reduced lung water content and plasma levels of tumor necrosis factor-α and interleukin-6 compared with vehicle controls. Most importantly, treatment with BI113823 significantly improved survival following severe sepsis in rats. CONCLUSIONS: Administration of B1 receptor antagonist BI113823 significantly reduced endotoxin-induced direct lung injury and also reduced sepsis-induced lung inflammatory response. Most importantly, BI113823 improved survival following severe polymicrobial sepsis.
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Lesión Pulmonar Aguda/tratamiento farmacológico , Bradiquinina/antagonistas & inhibidores , Citocinas/metabolismo , Dexametasona/uso terapéutico , Macrófagos/efectos de los fármacos , Lesión Pulmonar Aguda/mortalidad , Lesión Pulmonar Aguda/fisiopatología , Animales , Western Blotting , Bradiquinina/administración & dosificación , Líquido del Lavado Bronquioalveolar/citología , Ciclooxigenasa 2/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Modelos Animales de Enfermedad , Inmunohistoquímica , Mediadores de Inflamación/metabolismo , Interleucina-1beta/efectos de los fármacos , Interleucina-1beta/metabolismo , Macrófagos/citología , Masculino , Ratones , Ratones Endogámicos BALB C , Distribución Aleatoria , Ratas , Ratas Wistar , Valores de Referencia , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Background and Objectives: Colorectal cancer (CRC) is a prevalent form of cancer worldwide. Recent studies suggest that postbiotics derived from probiotic bacteria have the potential as an adjunct therapy for CRC. This study investigates the anti-cancer effects of Bifidobacterium breve (B. breve) and Lactobacillus rhamnosus (L. rhamnosus) postbiotics on the HT-29 cell line. Materials and Methods: Through MTT and scratch assay, we investigated the anti-proliferation and anti-migration effects of B. breve and L. rhamnosus postbiotics on HT-29 cells. Furthermore, postbiotic-mediated apoptosis was assessed by analyzing the expression of Bax, Bcl-2, and caspase-3. We also investigated the effects of B. breve postbiotics on the expression of three important genes involved in metastasis, including RSPO2, NGF, and MMP7. Consequently, we validated the expression of selected genes in twelve adenocarcinoma tissues. Results: The results demonstrated the significant impact of postbiotics on HT-29 cells, highlighting their ability to induce anti-proliferation, anti-migration, and apoptosis-related effects. Notably, these effects were more pronounced using B. breve postbiotics than L. rhamnosus. Additionally, B. breve postbiotics could inhibit metastasis through upregulation of RSPO2 while downregulating NGF and MMP7 expression in HT-29 cells. Conclusion: Our research suggests that postbiotic metabolites may be effective biological products for the prevention and treatment of cancer.
RESUMEN
Ziziphus Jujuba Mill (Z.J) is a well-known ethnomedical source of biologically active compounds with anti-inflammatory effects. However, its significance in acute lung injury (ALI) has never been studied. The present study aimed to explore whether Z.J could attenuate lipopolysaccharide (LPS)-induced inflammatory responses in an experimental model of ALI. Male BALB/c mice received an intratracheal administration of LPS (n=32) or phosphate buffer saline (PBS) (control, n=8). Within 1, 11, and 23 h post-LPS injection, mice were randomly assigned to receive intraperitoneal treatments of saline, dexamethasone (2 mg/kg), and 100 and 200 mg/kg of Z.J extracts, respectively. 24 h after intratracheal administration of LPS, bronchoalveolar lavage fluid and lung tissues were harvested and assessed for inflammatory cell influx, tumor necrosis factor-α (TNF-α) levels, and histological assessments. Treatment with Z.J extracts (100 and 200 mg/kg) and dexamethasone effectively reduced LPS-induced neutrophil and other inflammatory cell influx into the lung tissue compared to the untreated group. additionally, both doses of Z.J extracts (100 and 200 mg/kg) significantly ameliorated the lung wet-to-dry ratio and histopathological damage. Furthermore, compared to the untreated ALI mice, Z.J extract at the highest dose could significantly reduce the TNF-α level. The present findings indicated that Z.J could effectively ameliorate LPS-induced ALI inflammatory responses and might be considered a promising alternative therapy for the ALI phenotype.
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Lesión Pulmonar Aguda , Ziziphus , Ratones , Masculino , Animales , Lipopolisacáridos/farmacología , Factor de Necrosis Tumoral alfa , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/patología , Pulmón/patología , Líquido del Lavado Bronquioalveolar , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Dexametasona/efectos adversos , Ratones Endogámicos BALB C , FN-kappa BRESUMEN
Colorectal cancer (CRC) is a prevalent and life-threatening cancer closely associated with the gut microbiota. Probiotics, as a vital microbiota group, interact with the host's colonic epithelia and immune cells by releasing a diverse range of metabolites named postbiotics. The present study examined the effects of postbiotics on CRC's prominent differentially expressed genes (DEGs) using in silico and in vitro analysis. Through single-cell RNA sequencing (scRNA-seq), we identified four DEGs in CRC, including secreted frizzled-related protein 1 (SFRP1), secreted frizzled-related protein 2 (SFRP2), secreted frizzled-related protein 4 (SFRP4), and matrix metallopeptidase 7 (MMP7). Enrichment analysis and ExpiMap, a novel deep learning-based method, determined that these DEGs are involved in the Wnt signaling pathway as a primary cascade in CRC. Also, spatial transcriptome analysis showed specific expression patterns of the SFRP2 gene in fibroblast cell type. The expression of selected DEGs was confirmed on CRC and normal adjacent tissues using Real-Time quantitative PCR (RT-qPCR). Moreover, we examined the effects of postbiotics extracted from Lactobacillus acidophilus (L. acidophilus) on the proliferation, migration, and cell cycle distribution of HT-29 cells using MTT, scratch, and flow cytometry assays. Our results showed that L. acidophilus postbiotics induce cell cycle arrest at G1 phase and also had anti-proliferative and anti-migration effects on HT-29 cells, while it did not exert anti-proliferative activity on control fibroblasts. Finally, we revealed that treating HT-29 cells with postbiotics can affect the expression of selected DEGs. We suggested that L. acidophilus postbiotics have therapeutic potential in CRC by modulating key genes in the Wnt pathway.
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Neoplasias Colorrectales , Vía de Señalización Wnt , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/metabolismo , Lactobacillus acidophilus , Proteínas Relacionadas con Frizzled SecretadasRESUMEN
BACKGROUND: Airway remodeling is an important pathological feature of chronic airway diseases, which leads to a progressive decline in lung function. The present study examined the anti-remodeling and anti- inflammatory effect of BIBF1000, a triple-tyrosine kinase inhibitor that targets VEGF, PDGF, and FGF receptor signaling in a mouse model of repeated ovalbumin (OVA) challenges. METHODS: Female Balb-c mice were immunized intraperitoneally on days 0 and 12 with 50 µg ovalbumin plus 1 mg of Al(OH)3 in 200 µl saline. Intranasal OVA challenges (20 µg/50 µl in PBS) were administered on days 26, 29, and 31, and were repeated twice a week for 3 months. Animals received vehicle or BIBF1000 (25 mg/kg, b.i.d.) through gavage from day 26 to the end of fourth month. On day 120, bronchoalveolar lavage (BAL) and lung tissue were collected for biochemical and immunohistological analysis. RESULTS: Compared to vehicle controls, treatment with BIBF1000 reduced the numbers of BAL eosinophils, macrophages, neutrophils, and lymphocytes by 70.0%, 57.9%, 47.5%, and 63.0%, respectively, and reduced IL-5 and IL-13 in BAL. Treatment with BIBF1000 reduced airway mucus secretion, peribronchial fibrosis, small airway, and pulmonary arterial wall thickness, compared to vehicle controls. Furthermore, treatment with BIBF1000 also reduced the expression of inflammatory mediators (TNF-α, IL-1ß, IL-5, IL-13, MMP-2, MMP-9, COX-2, and iNOS) and inhibited ERK and AKT phosphorylation. CONCLUSIONS: The protective effect afforded by triple-tyrosine kinase inhibition with BIBF1000 in reducing allergen-induced airway and arterial remodeling was associated with down-regulation of inflammatory mediators, as well as inhibition of ERK and AKT signaling pathways.
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Alérgenos , Interleucina-13 , Remodelación Vascular , Animales , Femenino , Ratones , Alérgenos/farmacología , Modelos Animales de Enfermedad , Mediadores de Inflamación/metabolismo , Interleucina-13/metabolismo , Interleucina-5/metabolismo , Pulmón/patología , Ratones Endogámicos BALB C , Ovalbúmina , Proteínas Tirosina Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , /farmacologíaRESUMEN
Traditional bulk sequencing methods are limited to measuring the average signal in a group of cells, potentially masking heterogeneity, and rare populations. The single-cell resolution, however, enhances our understanding of complex biological systems and diseases, such as cancer, the immune system, and chronic diseases. However, the single-cell technologies generate massive amounts of data that are often high-dimensional, sparse, and complex, thus making analysis with traditional computational approaches difficult and unfeasible. To tackle these challenges, many are turning to deep learning (DL) methods as potential alternatives to the conventional machine learning (ML) algorithms for single-cell studies. DL is a branch of ML capable of extracting high-level features from raw inputs in multiple stages. Compared to traditional ML, DL models have provided significant improvements across many domains and applications. In this work, we examine DL applications in genomics, transcriptomics, spatial transcriptomics, and multi-omics integration, and address whether DL techniques will prove to be advantageous or if the single-cell omics domain poses unique challenges. Through a systematic literature review, we have found that DL has not yet revolutionized the most pressing challenges of the single-cell omics field. However, using DL models for single-cell omics has shown promising results (in many cases outperforming the previous state-of-the-art models) in data preprocessing and downstream analysis. Although developments of DL algorithms for single-cell omics have generally been gradual, recent advances reveal that DL can offer valuable resources in fast-tracking and advancing research in single-cell.
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Aprendizaje Profundo , Transcriptoma , Genómica/métodos , Aprendizaje Automático , Perfilación de la Expresión GénicaRESUMEN
OBJECTIVES: Acute lung injury (ALI) is a life-threatening pulmonary dysfunction associated with severe inflammation. There are still no effective pharmacological therapies for the treatment of ALI. In this concern, several anti-inflammatory agents could be used as add-on therapy to inhibit inflammation. Achillea wilhelmsii (AW) C. Koch is a well-known medicinal plant in the Iranian ethnomedical practices with anti-inflammatory activity. This study was aimed to evaluate the efficacy of ethanolic extract of AW on lipopolysaccharide (LPS)-induced ALI in mice. METHODS: The ALI model was established via the intra-tracheal (i.t.) administration of LPS (2 mg/kg) to male BALB/c mice. The ALI mice were divided into four groups (n=8 each) which intra-peritoneally (i.p.) treated with repeated doses of saline (model), dexamethasone (2 mg/kg), and AW (150-300 mg/kg) 1, 11 and 23 h post LPS administration. Twenty-four hours after the LPS challenge, bronchoalveolar lavage fluid (BALF) and lung tissue were evaluated for inflammatory cell influx, level of tumor necrosis factor-α (TNF-α) and histopathological changes. RESULTS: The AW (150-300 mg/kg) treated mice showed lower inflammatory cells infiltration in BALF and TNF-α level when compared to the model group. In addition, LPS induced several pathological alterations such as edema, alveolar hemorrhage and inflammatory cell infiltration into the interstitium and alveolar spaces. Treatment with AW significantly reduced LPS-induced pathological injury. CONCLUSIONS: Taken together, the data here indicated that AW may be considered as a promising add-on therapy for ALI.
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Achillea , Lesión Pulmonar Aguda , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/patología , Animales , Antiinflamatorios/efectos adversos , Inflamación/tratamiento farmacológico , Irán , Lipopolisacáridos/efectos adversos , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/efectos adversos , Factor de Necrosis Tumoral alfaRESUMEN
Immunotherapy has revolutionized cancer treatment and brought new aspects into tumor immunology. Effective immunotherapy will require using the suitable target antigens, optimizing the interaction between the antigenic peptide, the APC, and the T cell, and the simultaneous inhibitor of the negative regulatory process that inhibits immunotherapeutic effects and develop resistance. Tumor heterogeneity and its microenvironment is the leading cause of resistance in patients. Recently by emerging the single-cell RNA sequencing technology and its combination with immunotherapy, now we can specifically evaluate the mechanism of tumors in the face of immunotherapy agents at the single-cell resolution by detecting the transcriptional activity of immune checkpoints, screening neoantigens with high transcription levels, identifying rare cells, and other important processes. This review focuses on scRNA-seq, particularly on its application in cancer immunotherapy.
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Antineoplásicos Inmunológicos/farmacología , Neoplasias/patología , Medicina de Precisión/métodos , Anticuerpos Monoclonales/farmacología , Vacunas contra el Cáncer/farmacología , Citocinas/farmacología , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Inmunoterapia Adoptiva/métodos , Análisis de Secuencia de ARN/métodos , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: Ovarian cancer (OC) is one of the worrisome gynecological cancers worldwide. Given its considerable mortality rate, it is necessary to investigate its oncogenesis. METHODS: In this study, we used systems biology approaches to describe the key gene modules, hub genes, and regulatory drugs associated with serous OC as the novel biomarkers using weighted gene co-expression network analysis (WGCNA). FINDINGS: Our findings have demonstrated that the blue module genes (r = 0.8, p-value = 1e-16) are involved in OC progression. Based on gene enrichment analysis, the genes in this module are frequently involved in biological processes such as the Cyclic adenosine monophosphate (cAMP) signaling pathway and the cellular response to transforming growth factor-beta stimulation. The co-expression network has been built using the correlated module's top hub genes, which are ADORA1, ANO9, CD24P4, CLDN3, CLDN7, ELF3, KLHL14, PRSS8, RASAL1, RIPK4, SERINC2, and WNT7A. Finally, a drug-target network has been built to show the interaction of the FDA-approved drugs with hub genes. CONCLUSIONS: Our results have discovered that ADORA1, ANO9, SERINC2, and KLHL14 are hub genes associated with serous OC. These genes can be considered as novel candidate target genes for treating OC.
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Redes Reguladoras de Genes , Neoplasias Ováricas , Claudinas , Bases de Datos Genéticas , Perfilación de la Expresión Génica/métodos , Humanos , Proteínas de la Membrana/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Biología de SistemasRESUMEN
Vitiligo is the most common cause of skin, hair, and oral depigmentation which is known as an autoimmune disorder. Genetic and environmental factors have important roles in the progression of the disease. Dysregulation of gene expression, like microRNAs (miRNA), may serve as major relevant factors. Several biological processes are involved in vitiligo disease and developing a comprehensive approach helps us to better understand the molecular mechanisms of disease. In this research, we describe how a weighted gene co-expression network analysis as a systems biology approach assists to define the primary gene modules, hub genes, and messenger RNA (mRNA)-miRNA regulatory network in vitiligo disease as the novel biomarkers. The results demonstrated a module with a high correlation with vitiligo state. Moreover, gene enrichment analysis showed that this module's genes were mostly involved in some biological activities including G protein-coupled receptors signaling pathway, lymphocyte chemotaxis, chemokine activity, neutrophil migration, granulocyte chemotaxis, etc. The co-expression network was constructed using top hub genes of the correlated module which are named as CXCL10, ARL9, AKR1B10, COX7B, RPL26, SPA17, NDUFAF2, RPF2, DAPL1, RPL34, CWC15, NDUFB3, RPL26L1, ACOT13, HSPB11, and NSA2. MicroRNAs prediction tool (miRWalk) revealed top miRNAs correlated with the interested module. Finally, a drug-target network was constructed which indicated interactions of some food and drug administration (FDA) approved drugs with hub genes. Our findings specified one important module and main hub genes which can be considered as novel biomarkers for vitiligo therapeutic purposes.
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Redes Reguladoras de Genes/genética , Vitíligo/genética , Biomarcadores/metabolismo , Biología Computacional/métodos , Perfilación de la Expresión Génica/métodos , Humanos , Proteínas de la Membrana/genética , MicroARNs/genética , Chaperonas Moleculares/genética , ARN Mensajero/genética , Transducción de Señal/genética , Biología de Sistemas/métodosRESUMEN
Bruton's tyrosine kinase (Btk) belongs to the Tec family of nonreceptor protein tyrosine kinases. Mutations in the BTK gene cause X-linked agammaglobulinemia (XLA); a primary immunodeficiency disorder in human. No clear genotype-phenotype correlation has been established in XLA so far. To determine how differently mutations in BTK affect the severity of the disease and if BTK promoter polymorphic variant or intron 1 polymorphic variant in Tec, a cytoplasmic tyrosine kinase that might substitute for Btk, could contribute to the clinical phenotype, we analyzed the clinical and molecular findings in a cohort of XLA patients. Polymorphisms in BTK promoter and TEC intron 1 regions include substitutions of C>T (rs2071219) and T>C (rs2664019), respectively. Btk expression was evaluated by means of western immunoblotting and fluorescence-activated cell sorter analysis. Mutations were categorized as mild or severe and patients were evaluated for the clinical severity of disease. On the basis of the results, severe genotypes do not necessarily lead to severe phenotypes. More over, in a considerable number of patients with mild phenotype we showed a severe mutation with a tendency toward C substitution in the polymorphic site on TEC intron 1.
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Agammaglobulinemia/genética , Proteínas Tirosina Quinasas/deficiencia , Agammaglobulinemia Tirosina Quinasa , Agammaglobulinemia/patología , Estudios de Cohortes , Análisis Mutacional de ADN , Salud de la Familia , Enfermedades Genéticas Ligadas al Cromosoma X , Genotipo , Humanos , Mutación , Fenotipo , Proteínas Tirosina Quinasas/genética , Índice de Severidad de la EnfermedadRESUMEN
Electrospun nanofibers that contain silver nanoparticles (AgNPs) have a strong antibacterial activity that is beneficial to wound healing. However, most of the literature available on the bactericidal effects of this material is based on the use of AgNPs with uncontrolled size, shape, surface properties, and degree of aggregation. In this study, we report the first versatile synthesis of novel catechol moieties presenting electrospun nanofibers functionalized with AgNPs through catechol redox chemistry. The synthetic strategy allows control of the size and amount of AgNPs on the surface of nanofibers with the minimum degree of aggregation. We also evaluated the rate of release of the AgNPs, the biocompatibility of the nanofibers, the antibacterial activity in vitro, and the wound healing capacity in vivo. Our results suggest that these silver-releasing nanofibers have great potential for use in wound healing applications.