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1.
Clin Respir J ; 18(4): e13742, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38664220

ABSTRACT

BACKGROUND: Allergic asthma is an important respiratory system problem characterized by airway inflammation, breathlessness, and bronchoconstriction. Allergic asthma and its outcomes are triggered by type 2 allergic immune responses. Tectorigenin is a methoxy-isoflavone with anti-inflammatory effects. In this study, we investigated the effects of tectorigenin on the pathophysiology of allergic asthma in an animal model. METHODS: Asthmatic mice were treated with tectorigenin. Then airway hyperresponsiveness (AHR), eosinophil percentage, levels of interleukin (IL)-33, IL-25, IL-13, IL-5, IL-4, total and ovalbumin (OVA)-specific immunoglobulin (Ig)E, and lung histopathology were evaluated. RESULT: Tectorigenin significantly (P 〈 0.05) reduced eosinophil infiltration (41 ± 7%) in the broncho-alveolar lavage fluid (BALF), serum IL-5 level (41 ± 5, pg/mL), and bronchial and vascular inflammation (scores of 1.3 ± 0.2 and 1.1 ± 0.3, respectively) but had no significant effects on AHR, serum levels of IL-33, -25, -13, and -4 (403 ± 24, 56 ± 7, 154 ± 11, and 89 ± 6 pg/mL, respectively), total and OVA-specific IgE (2684 ± 265 and 264 ± 19 ng/mL, respectively), goblet cell hyperplasia, and mucus production. CONCLUSION: Tectorigenin could control inflammation and the secretion of inflammatory mediators of asthma, so it can be regarded as a potential antiasthma treatment with the ability to control eosinophilia-related problems.


Subject(s)
Anti-Inflammatory Agents , Antioxidants , Asthma , Disease Models, Animal , Isoflavones , Mice, Inbred BALB C , Ovalbumin , Animals , Asthma/drug therapy , Asthma/chemically induced , Asthma/metabolism , Asthma/immunology , Asthma/pathology , Mice , Ovalbumin/toxicity , Ovalbumin/adverse effects , Isoflavones/pharmacology , Isoflavones/therapeutic use , Antioxidants/pharmacology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Immunoglobulin E/blood , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Female , Lung/pathology , Lung/drug effects , Lung/metabolism , Lung/immunology , Cytokines/metabolism
2.
Cytokine ; 175: 156479, 2024 03.
Article in English | MEDLINE | ID: mdl-38199086

ABSTRACT

Congestive heart failure (CHF) is a complex multistage syndrome that has a great financial burden on human societies. It was known that the damaged myocardium sends a signal to stimulate the immune system and proliferation of leukocytes. In continuous, cytokine storm can be initiated and causes the probability of CHF. Persistent inflammation by increasing the levels of pro-inflammatory cytokines, plays an important role in the pathogenesis of CHF and causes remodeling, which is a progressive processs. Although treatment by drugs can reduce mortality and partially control the symptoms of heart failure patients, but complications and mortality are still high. Therefore, other treatment options such as Cardiac Resynchronization Therapy (CRT) are necessary. Today, it is known that CRT can be an effective treatment for many patients with heart failure. CRT is novel, non-pharmacological, and device-based therapy that would be beneficial to know more about its performance in the management of heart failure. In this study, we have reviewed the immunological processes involved in heart failure and the effect of CRT in controlling of the cytokine storm.


Subject(s)
Cardiac Resynchronization Therapy , Heart Failure , Humans , Cytokines , Cytokine Release Syndrome/therapy , Heart Failure/therapy , Treatment Outcome
3.
Regen Ther ; 25: 157-161, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38178929

ABSTRACT

Asthma is a pulmonary disease and its pathophysiology includes inflammation, obstruction, edema of the airways, and mucus secretions in the airways. Mesenchymal stem cells (MSCs) are self-renewal that use the therapeutic potential of these cells can be applied as treatments of asthma. In this study, the effect of Mesenchyme stem cells on asthma was investigated. MSCs were administrated for asthmatic mice and then, percentage of eosinophils in blood and bronchoalveolar lavage fluid (BALF), levels of interleukine (IL)-4 and Immunoglubolin (Ig)E were measured. Also histopathological study of lung tissue was done. MSCs administration could control percentage of eosinophils in blood and BALF, levels of IgE and IL-4, eosinophilic inflammation, mucin realizing and goblet cell hyper-plasia. Administration of MSCs as treatment of asthma can be a useful and applicable therapy in control of asthma symptoms.

4.
ESC Heart Fail ; 10(6): 3250-3257, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37776150

ABSTRACT

N terminal pro brain natriuretic peptide (NT-proBNP) plays an important role in the diagnosis and prognosis of heart failure (HF). The plasma level of NT-proBNP in atrial fibrillation (AF) patients was higher than of sinus rhythm patients. In HF, NT-proBNP levels are affected by the concomitant presence of AF, making it difficult to distinguish between HF and AF in patients with elevated NT-proBNP. Several other diseases, such as renal failure and pulmonary embolism, are known to further increase NT-proBNP levels in patients with concomitant HF. Therefore, NT-proBNP is a sensitive but non-specific marker for the detection of HF. AF is very important in this regard because among patients with HF regardless of ejection fraction, symptoms such as shortness of breath and atrial enlargement develop and can mimic HF. In the present study, we investigated whether the prognostic value of natriuretic peptides in HF holds true for patients with concomitant AF.


Subject(s)
Atrial Fibrillation , Heart Failure , Humans , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Heart Failure/complications , Heart Failure/diagnosis , Natriuretic Peptide, Brain , Peptide Fragments
5.
JAMA Oncol ; 9(10): 1401-1416, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37676656

ABSTRACT

Importance: Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning. Objective: To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates. Evidence Review: The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019. Findings: In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia. Conclusions and Relevance: In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.


Subject(s)
Global Burden of Disease , Pharyngeal Neoplasms , Adult , Female , Humans , Male , Global Health , Incidence , Lip , Pharyngeal Neoplasms/epidemiology , Quality-Adjusted Life Years , Risk Factors , Tobacco Use/epidemiology
6.
Allergol Immunopathol (Madr) ; 51(3): 111-116, 2023.
Article in English | MEDLINE | ID: mdl-37169568

ABSTRACT

Allergic rhinitis (AR) is a common atopic problem in which immune response to the environmental factors leads to clinical symptoms. Helicobacter pylori neutrophil-activating protein (HP-NAP) as a peptide attenuates Th2 response and stimulates Th1 activation and mucus adhesion promoting protein (MapA) as a cell-surface protein binds to mucus. This study evaluated the effect of HP-NAP and MapA conjugated with alumina nanoparticle on AR. HP-NAP and HP-NAP with MapA were conjugated to alumina nanoparticle and two separate nanoparticles were produced. The AR mice were treated with these and HP-NAP in peptide form. The AR symptoms, gene expression of mucus, levels of IL-33 and IL-4, and total and ovalbumin (OVA)-specific IgE levels were evaluated. Nasal rubbing, sneezing, gene expression of mucus, and IL-33 and IL-4 levels, and OVA-specific and total IgE were decreased in three treated groups compared to AR, and there was a significant decrease in the symptoms in AR-H-M-A group (P < 0.05) when compared to the other treated groups. HP-NAP has a controlling effect on AR, and in nanoparticle-conjugated form it can strongly attach to the airway's mucus via MapA. Therefore, cooperation of HP-NAP-alumina with MapA can produce an effective and applicable treatment for AR.


Subject(s)
Interleukin-33 , Rhinitis, Allergic , Animals , Mice , Interleukin-4 , Th2 Cells , Ovalbumin , Immunoglobulin E/metabolism , Anti-Inflammatory Agents/therapeutic use , Mice, Inbred BALB C , Disease Models, Animal , Cytokines/metabolism , Nasal Mucosa/metabolism
7.
Allergol Immunopathol (Madr) ; 51(2): 45-51, 2023.
Article in English | MEDLINE | ID: mdl-36916087

ABSTRACT

Asthma is an important pulmonary disease associated with T helper lymphocyte (Th)2 dominant immune response, which can initiate allergic and inflammatory reactions. Interleukin (IL)-10 is the main immune suppressor cytokine, and mesenchymal stem cells (MSCs) have an immune-modulatory potential that can be transduced with the expression of the IL-10 gene to control pathophysiology of allergic asthma. Bone marrow's MSCs were isolated and transduced with the expression vector that contains the expressible IL-10 gene. Then, allergic asthma mouse model was produced and treated with manipulated MSCs. Methacholine challenge test; measurement of IL-4, IL-5, IL-8, IL-13, IL-25, and IL-33; and total and ovalbumin (OVA)-specific immunoglobulin (Ig)E levels were done. Hyperplasia of the goblet cell, secretion of mucus, and peribronchiolar and perivascular eosinophilic inflammation were evaluated in lung pathological sections. IL-25, IL-33, and total IgE levels; AHR; eosinophilic inflammation; hyperplasia of the goblet cell; and secretion of mucus could be controlled in M, MV, and MV-10 groups, and the control in the MV-10 group was strong compared to M and MV groups. MSCs have immune-modulatory capacity that can control allergic asthma pathophysiology, and this effect can be strengthened and reinforced by the expression of IL-10 gene.


Subject(s)
Asthma , Eosinophilia , Mesenchymal Stem Cells , Animals , Mice , Asthma/genetics , Asthma/therapy , Bronchoalveolar Lavage Fluid , Cytokines , Disease Models, Animal , Hyperplasia/pathology , Immunoglobulin E , Inflammation , Interleukin-10/genetics , Interleukin-33 , Lung/pathology , Mice, Inbred BALB C , Ovalbumin
8.
Allergol. immunopatol ; 51(2): 45-51, 01 mar. 2023. ilus, graf
Article in English | IBECS | ID: ibc-216797

ABSTRACT

Asthma is an important pulmonary disease associated with T helper lymphocyte (Th)2 dominant immune response, which can initiate allergic and inflammatory reactions. Interleukin (IL)-10 is the main immune suppressor cytokine, and mesenchymal stem cells (MSCs) have an immune-modulatory potential that can be transduced with the expression of the IL-10 gene to control pathophysiology of allergic asthma. Bone marrow’s MSCs were isolated and transduced with the expression vector that contains the expressible IL-10 gene. Then, allergic asthma mouse model was produced and treated with manipulated MSCs. Methacholine challenge test; measurement of IL-4, IL-5, IL-8, IL-13, IL-25, and IL-33; and total and ovalbumin (OVA)-specific immunoglobulin (Ig)E levels were done. Hyperplasia of the goblet cell, secretion of mucus, and peribronchiolar and perivascular eosinophilic inflammation were evaluated in lung pathological sections. IL-25, IL-33, and total IgE levels; AHR; eosinophilic inflammation; hyperplasia of the goblet cell; and secretion of mucus could be controlled in M, MV, and MV-10 groups, and the control in the MV-10 group was strong compared to M and MV groups. MSCs have immune-modulatory capacity that can control allergic asthma pathophysiology, and this effect can be strengthened and reinforced by the expression of IL-10 gene (AU)


Subject(s)
Animals , Male , Mice , Cell- and Tissue-Based Therapy , Genetic Therapy , Asthma/therapy , Hypersensitivity/therapy , Interleukin-10 , Mesenchymal Stem Cells , Disease Models, Animal , Mice, Inbred BALB C , Cells, Cultured , Transduction, Genetic
9.
J Investig Med ; 71(3): 235-243, 2023 03.
Article in English | MEDLINE | ID: mdl-36803044

ABSTRACT

Asthma is a complex respiratory disease, which is controlled by genetic and environmental factors. Type 2-dominant immune response is responsible for asthma. Decorin (Dcn) and stem cells have modulatory effect on immune system and may control tissue remodeling and asthma pathophysiology. In this study, immunomodulatory effect of transduced induced pluripotent stem cells (iPSCs) with expression of Dcn gene on allergic asthma pathophysiology was evaluated. After transduction of iPSCs with Dcn gene, allergic asthma mice were treated with iPSCs and transduced iPSCs via intrabronchial. Then, airway hyperresponsiveness (AHR), levels of interleukin (IL)-4, IL-5, IL-13, IL-33, total IgE, leukotrienes (LTs) B4, C4, hydroxyproline (HP) content, and transforming growth factor-beta (TGF-ß) were measured. Also, lung histopathology study was done. AHR, levels of IL-4, IL-5, IL-13, IL-33, total IgE, LTs B4, C4, TGF-ß, HP content, mucus secretion, goblet cell hyperplasia, and eosinophilic inflammation were controlled by iPSCs and transduced iPSCs treatment. Therapeutic effect of iPSCs could control main allergic asthma symptoms and related pathophysiologic mechanisms and the effect can be increased when applied with Dcn expression gene.


Subject(s)
Asthma , Induced Pluripotent Stem Cells , Mice , Animals , Interleukin-33 , Decorin/genetics , Interleukin-13/metabolism , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/pathology , Interleukin-5/metabolism , Lung/pathology , Asthma/genetics , Transforming Growth Factor beta/metabolism , Immunoglobulin E , Disease Models, Animal , Mice, Inbred BALB C , Cytokines/metabolism
10.
Allergol Immunopathol (Madr) ; 51(1): 110-115, 2023.
Article in English | MEDLINE | ID: mdl-36617829

ABSTRACT

Asthma is a chronic airway disease. Allergic reactions and T helper (h)2 immune response play a key role in asthma occurrence. Cell therapy can control inflammation and remodeling responses in allergic asthma, and cytokines can change this effect. Therefore, in this study, the effect of treated cell therapy with IL-2 to control allergic asthma was studied. Bone marrow cells were extracted and co-cultured with IL-2 and the cells were used via intra-tracheal administration in allergic asthma mice. Levels of IL-4, IL-5, IL-13, Leukotriene B4 and C4, and remodeling factors were measured. At least, a histopathology test of lung tissue was done. Type2 cytokines, leukotrienes, remodeling factors, mucus secretion, goblet cell hyperplasia, peri-bronchial and peri-vascular inflammation were significantly (p˂0.05) decreased by treating with bone marrow-derived mononuclear cells (BMDMCs) and IL-2-BMDMCs. Treatment with IL-2-BMDMCs could significantly decrease IL-13, transforming growth factor (TGF)-ß, HP levels, and mucus secretion (p˂0.05) compared to BMDMCs treatment. In this study, BMDMCs and IL-2-BMDMCs therapy could decrease inflammation, allergic, and remodeling factors in allergic asthma. Cell therapy with BMDMCs had a strong and notable effect on the control of allergic asthma pathophysiology when co-cultured and used with IL-2.


Subject(s)
Asthma , Hypersensitivity , Interleukin-2 , Leukocytes, Mononuclear , Animals , Mice , Asthma/pathology , Bone Marrow , Bronchoalveolar Lavage Fluid , Cytokines/metabolism , Disease Models, Animal , Hypersensitivity/pathology , Inflammation/pathology , Interleukin-13 , Interleukin-2/pharmacology , Lung/pathology , Mice, Inbred BALB C , Ovalbumin , Transforming Growth Factor beta
11.
J Investig Med ; 71(2): 71-80, 2023 02.
Article in English | MEDLINE | ID: mdl-36647329

ABSTRACT

The pandemic of COVID-19 in worldwide causes recent millions of morbidity and mortality in all countries and is the most important challenge in the world in recent years. Coronavirus is a single-stranded RNA virus and infection with COVID-19 leads to acute respiratory distress syndrome, lung inflammation, cytokine storm, and death. The other complications include endothelial dysfunction, activation of coagulation, thromboembolic events, and vascular disease. Cardiovascular complications such as myocardial and stroke ischemia, pulmonary thromboembolism, systemic arterial, and deep vein thrombosis were reported. In this review, we presented immuno-pathological mechanisms and the effects of COVID-19 on the cardiovascular system, heart, vessels, coagulation system, and molecular glance of immuno-inflammation to the COVID-19's pathology on the cardiovascular system.


Subject(s)
COVID-19 , Cardiovascular Diseases , Thromboembolism , Humans , COVID-19/complications , Cardiovascular Diseases/complications , SARS-CoV-2 , Thromboembolism/etiology , Inflammation/complications
12.
J Drug Target ; 31(3): 296-309, 2023 03.
Article in English | MEDLINE | ID: mdl-36398476

ABSTRACT

In this study, epithelial cell adhesion molecule (EpCAM) aptamer-activated nanoparticles (Ap-NPs) were synthesised to enhance treatment efficiency in colorectal cancer (CRC). PLGA [poly(d, l-lactide-co-glycolide)] copolymer was fabricated by conjugation of COOH-PEG-NH2 to PLGA-COOH through an EDC/NHS-mediated chemistry. Afterwards, 5-fluorouracil-loaded (FU) nanoparticles were prepared using the water/oil/water double emulsion solvent evaporation method. The in vitro cytotoxicity of formulations was evaluated using the MTT assay in HCT-116, CT-26 and HEK-293 cell lines. For in vivo study, tumour-bearing BALB/c mice were established by subcutaneous injection of CT-26 cell line. The results indicated that fabricated AP-FU-NPs had 101 nm size with a spherical surface, relatively homogeneously and, satisfactory encapsulation efficiency (83.93%). In vitro experiments revealed that Ap-FU-NPs had a superior in vitro cytotoxicity than both FU-NPs and free 5-FU in CT-26 and HCT-116 cells but, were significantly low toxic against HEK-293 cells relative to free 5-FU. Furthermore, in vivo results showed no significant haemolytic effect, hepatic and renal injury, or weight loss. After treatment of various animal groups with formulations, notable tumour growth delay was observed following the order: Ap-FU-NPs < FU-NPs < 5-FU < PBS. The results suggest that AP-FU-NPs could be an effective and promising carrier for 5-FU delivery to the EpCAM overexpressing CRC cells.


Subject(s)
Drug Carriers , Nanoparticles , Mice , Animals , Humans , Epithelial Cell Adhesion Molecule , Drug Carriers/chemistry , HEK293 Cells , Fluorouracil/pharmacology , Fluorouracil/therapeutic use , Nanoparticles/chemistry , Particle Size , Cell Line, Tumor
13.
Fundam Clin Pharmacol ; 37(2): 340-346, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36314138

ABSTRACT

Allergic rhinitis as common airway disease has high prevalence in all peoples worldwide. In allergic diseases, Th2 cells release type 2 cytokines that support the inflammation in airways. All the drugs used for allergic rhinitis do not cure completely, and the choice of drugs according to cost and efficacy is very important in all groups of atopic patients. Therefore, in this study, the effect of commercial drugs on cytokine gene expression has been studied. Male Balb/c mice were divided into six groups. Allergic rhinitis was induced in five of the six groups with ovalbumin, and four of these five groups were treated with salbutamol, budesonide, theophylline, and montelukast. The fifth group was used as positive control group and the sixth group as negative control group. For the survey, RNA was extracted, cDNA was synthesized, and quantitative real-time PCR was done for 21 genes. The four drugs had different effects on mRNA expression of cytokines (IL-1b, 2, 4, 5, 7, 8, 9, 11, 12, 13, 17, 18, 22, 25, 31, 33, 37, IFN-γ, TNF-α, TGF-ß1, and eotaxin) in the allergic rhinitis groups. Salbutamol can be used during pregnancy and breastfeeding, but it has some side effects. Budesonide in the inhaled form is generally safe in pregnancy. Theophylline cannot control allergic attack in the long run. Montelukast is not useful in the treatment of acute allergic attacks. Immunomodulatory and anti-inflammatory effects of drugs in control of allergic rhinitis via Th2 cytokines can be new approaches in molecular medicine.


Subject(s)
Cytokines , Rhinitis, Allergic , Animals , Mice , Male , Cytokines/genetics , Cytokines/metabolism , Theophylline/therapeutic use , Rhinitis, Allergic/drug therapy , Budesonide/pharmacology , Budesonide/therapeutic use , Albuterol/therapeutic use , Gene Expression , Ovalbumin , Mice, Inbred BALB C , Disease Models, Animal
14.
ESC Heart Fail ; 10(2): 1418-1421, 2023 04.
Article in English | MEDLINE | ID: mdl-36347818

ABSTRACT

Complete heart block (CHB) is a serious health condition, and polyarteritis nodosa (PAN) is an important autoimmune disease. In the COVID-19 pandemy, several vaccines were developed for the COVID-19 disease that shown several side effects, and some of these complications are still unknown. This is the first report of CHB in a patient with history of PAN after COVID-19 vaccination. A 68-year-old man with a history of PAN referred to our hospital, complaining of presyncope episodes and dizziness after receiving a COVID-19 vaccine. Physical examination, laboratory tests, and transthoracic echocardiography were normal. In his electrocardiogram, a narrow QRS complex, AV dissociation, and junctional escape rhythm were seen. Coronary angiography showed a mild coronary artery disease. The patient, suffering from PAN for years, was hypothesized due to CHB a few days after COVID-19 vaccination. This case report suggests that COVID-19 vaccines may interrupt the conduction system of the heart and the fact that underlying PAN may predispose to CHB following COVID-19 vaccination. Further studies are needed to accurately assess a possible association between PAN, CHB, and COVID-19 vaccines.


Subject(s)
COVID-19 Vaccines , COVID-19 , Polyarteritis Nodosa , Aged , Humans , Male , COVID-19/complications , COVID-19 Vaccines/adverse effects , Heart Block/etiology , Heart Block/complications , Polyarteritis Nodosa/complications , Polyarteritis Nodosa/diagnosis , Vaccination/adverse effects
15.
Fundam Clin Pharmacol ; 37(1): 116-124, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35959714

ABSTRACT

Asthma is a common respiratory disease that has no definitive treatment at now. Immune response shifting from T helper (Th)1 to the Th2 is a main problem in asthma, and immunomodulation can help to control asthma. IL-35 and mesenchymal stem cells (MSCs) have regulatory effect on the immune system and may have the ability to control asthma pathology. After culturing MSCs, expression vector of IL-35 (pUNO1-mIL35elasti) was transduced to the MSCs, and then, asthmatic mice were treated with MSCs, MSCs-vector, MSCs-vector-IL-35, and no treatment. Airway hyperresponsiveness (AHR), levels of the cytokines, total and ovalbumin (OVA) specific immunoglobulin (Ig)E, LTB4, and LTC4 were measured. Lung tissue histopathology was also done. MSCs were successfully transduced by pUNO1-mIL35elasti vector, and IL-35 was produced in transduced cells. AHR, levels of the cytokines, IgEs, LTs, goblet cell hyperplasia, mucus secretion, peribronchial, and perivascular inflammation were controlled by MSCs therapy. In MSCs-IL-35 group, these controls were stronger than MSCs without IL-35 group. MSCs had strong effect on control of asthma. Transfected MSCs by expressing IL-35 gene could significantly better control allergic asthma symptoms than MSCs without IL-35. In the future, identification of the IL-35 mechanism of action would be useful to improve cytokine-cell based therapies.


Subject(s)
Asthma , Mesenchymal Stem Cells , Animals , Mice , Asthma/therapy , Asthma/genetics , Lung/metabolism , Cytokines/metabolism , Immunoglobulin E , Immunity , Interleukins/genetics , Mesenchymal Stem Cells/metabolism , Immunomodulation , Ovalbumin , Mice, Inbred BALB C , Bronchoalveolar Lavage Fluid , Disease Models, Animal
16.
Allergol Immunopathol (Madr) ; 50(6): 71-75, 2022.
Article in English | MEDLINE | ID: mdl-36335448

ABSTRACT

Allergic rhinitis and asthma are the main airway diseases with a higher prevalence. Eosinophilic inflammation, airway hyperresponsiveness, mucus hypersecretion, and reversible airflow obstruction are immunopathogenesis symptoms of rhinitis and asthma. Crotonic acid has bio-activity on the inflammation, and gluconic acid as chelator may protect crotonic acid activity in airway and together may control allergic rhinitis and asthma.Allergic rhinitis and asthma mice models were treated with crotonic and gluconic acids. The total IgE, histamine, IL-4, IL-5, and IL-13 levels were measured. In lung tissues, goblet cell hyperplasia, mucus hypersecretion, and inflammation were evaluated.The level of IL-5, goblet cell hyperplasia, and perivascular and peribronchial inflammation were controlled by crotonic acid in asthma and allergic rhinitis groups. But, total IgE, hista-mine, IL-4, and IL-13 levels, and mucus hypersecretion had no significant changes between treated and nontreated asthma and rhinitis groups.


Subject(s)
Asthma , Rhinitis, Allergic , Rhinitis , Mice , Animals , Interleukin-13 , Interleukin-4 , Crotonates/therapeutic use , Amides/therapeutic use , Hyperplasia , Interleukin-5 , Asthma/drug therapy , Asthma/pathology , Rhinitis, Allergic/drug therapy , Immunoglobulin E , Inflammation , Anti-Inflammatory Agents/therapeutic use , Disease Models, Animal , Cytokines , Bronchoalveolar Lavage Fluid
17.
Avicenna J Phytomed ; 12(5): 527-536, 2022.
Article in English | MEDLINE | ID: mdl-36249456

ABSTRACT

Objective: Allergic asthma is a complex inflammatory disorder that affects the airways. As an ancient medical system, Iranian Traditional Medicine (ITM) recommends a polyherbal formula called "Monzej-e-balgham" for the treatment of asthma. In the present investigation, the antiasthmatic effects of "Monzej-e-balgham" were examined in a murine model of allergic asthma. Materials and Methods: Twenty-eight Balb/c mice weighing 15-20 g were allocated into 4 groups. As negative and positive controls, groups I and II received phosphate-buffered saline (PBS) and ovalbumin (OVA) solutions, respectively. Groups III and IV were first sensitized with OVA and then respectively treated with "Monzej-e-balgham" (63 mg/kg) and budesonide. Finally, bronchoalveolar lavage fluid (BALF) and lung tissues of the animals were collected and used for eosinophil counting, Th2 type interleukins (IL-5, IL-13, and IL-33) measurement, and histological examinations. Results: "Monzej-e-balgham" significantly reduced the number of eosinophils and the levels of IL-5, IL-13, and IL-33 in BALF specimens compared to OVA-sensitized group (p<0.05). It also ameliorated histopathological changes of the lung tissues such as goblet cells hyperplasia and mucus overproduction in comparison to group II. Interestingly, the results of the "Monzej-e-balgham"-treated group were comparable with those obtained for budesonide-inhaled mice. Conclusion: The present data indicated a mechanism that involves Th2 inflammatory responses in allergic asthma and suggested a polyherbal mixture for the treatment of this disease.

18.
ACS Biomater Sci Eng ; 8(10): 4566-4576, 2022 10 10.
Article in English | MEDLINE | ID: mdl-36054652

ABSTRACT

Asthma is a common chronic lung disease without absolute treatment, and hypersensitivity reactions and type 2 immune responses are responsible for asthma pathophysiology. ADAM10 as a metalloproteinase transmembrane protein is critical for development of Th2 responses, and levamisole as an anthelmintic drug has immunomodulatory effects, which not only regulates ADAM10 activity but also can suppress the bone marrow and neutrophil production. Therefore, in the present study, nanoparticles were used as a levamisole delivery system to reduce bone marrow suppression, and the immunomodulatory and ADAM10 inhibitory effects of levamisole were studied in allergic asthma. Asthmatic mice were treated with PLGA-levamisole nanoparticles. Then, AHR, BALF, and blood cell counts, levels of the IgG1 subclass, total and OVA-specific IgE, IL2, IL-4, IL-5, IL-10, IL-13, IL-17, IL-25, IL-33, INF-γ, and TNF-α, gene expression of FoxP3, T-bet, RORγt, PU.1, GATA3, FcεRII, CysLT1R, eotaxin, and ADAM10, and lung histopathology were evaluated. PLGA-LMHCl with considered characteristics could control airway hyper-responsiveness, eosinophils in the BALF, levels of immunoglobulins, Th2-, Th9-, and Th17-derived cytokines and pivotal genes, eosinophilic inflammation, hyperplasia of the goblet cell, and hyperproduction of mucus and could increase Th1- and Treg-derived cytokines and also pivotal genes. It could also modulate the ADAM10 activity and had no effect on the number of neutrophils in the bloodstream. The novel safe nanodrug had no side effect on the bone marrow to produce neutrophils and could control the allegro-immuno-inflammatory response of asthma.


Subject(s)
Asthma , Nanoparticles , ADAM10 Protein , Amyloid Precursor Protein Secretases , Animals , Asthma/drug therapy , Asthma/metabolism , Bronchoalveolar Lavage Fluid , Cytokines/metabolism , Forkhead Transcription Factors/metabolism , Forkhead Transcription Factors/pharmacology , Forkhead Transcription Factors/therapeutic use , Immunoglobulin E/pharmacology , Immunoglobulin E/therapeutic use , Immunoglobulin G/pharmacology , Immunoglobulin G/therapeutic use , Immunologic Factors/pharmacology , Immunologic Factors/therapeutic use , Interleukin-10/pharmacology , Interleukin-10/therapeutic use , Interleukin-13/pharmacology , Interleukin-13/therapeutic use , Interleukin-17/pharmacology , Interleukin-17/therapeutic use , Interleukin-2/pharmacology , Interleukin-2/therapeutic use , Interleukin-33/pharmacology , Interleukin-33/therapeutic use , Interleukin-4/pharmacology , Interleukin-4/therapeutic use , Interleukin-5/pharmacology , Interleukin-5/therapeutic use , Levamisole/pharmacology , Levamisole/therapeutic use , Lung/pathology , Membrane Proteins , Mice , Nanoparticles/therapeutic use , Nuclear Receptor Subfamily 1, Group F, Member 3/therapeutic use , Ovalbumin/pharmacology , Ovalbumin/therapeutic use , Tumor Necrosis Factor-alpha/pharmacology , Tumor Necrosis Factor-alpha/therapeutic use
19.
ESC Heart Fail ; 9(6): 3785-3790, 2022 12.
Article in English | MEDLINE | ID: mdl-35975554

ABSTRACT

Allergic asthma is an inflammatory disorder of the bronchi, and as a major health problem, more than 350 million people suffer from asthma in the world. Many cardiovascular disorders resulted in the impairment of the heart's power to pump blood that leads to the HF. More than 25 million people worldwide live with HF. Accordingly, identifying the biomarkers to predict the onset of future asthma and HF is necessary. IL-33 is an inflammatory cytokine that has the main role in pathophysiology of asthma and HF. Also, in IL-33 receptor, the ST2 is involved in cardiac fibrosis and remodelling in HF and pathogenesis of allergic asthma. Increased sST2 in allergic asthma helps to control inflammation during asthma, but increased sST2 in HF is a predictable biomarker to present risk factor of HF during the time of the patients.


Subject(s)
Asthma , Heart Failure , Humans , Interleukin-33/metabolism , Interleukin-1 Receptor-Like 1 Protein , Biomarkers , Heart Failure/diagnosis , Heart Failure/etiology , Asthma/complications , Asthma/diagnosis , Inflammation
20.
Fundam Clin Pharmacol ; 36(6): 1005-1010, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35763864

ABSTRACT

Chronic obstructive pulmonary disease (COPD) as an inflammatory respiratory system disease is caused by exposure to cigarette smoke and tobacco in long-term. Some anti-inflammatory peptides can control inflammation in COPD. N-acetyl-seryl-aspartyl-proline (Ac-SDKP) and vasoactive intestinal peptide (VIP) as peptide have anti-inflammatory effect, and, in this study, the effect of Ac-SDKP and VIP on COPD inflammation was studied. After producing cigarette smoke-induced COPD mice model, which were treated with VIP and Ac-SDKP, the levels of antioxidant-related factors (malondialdehyde (MDA) and superoxide dismutase (SOD)), fibrotic factors (hydroxyproline (HP) and TGF-ß), pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6), and inflammation in histopathological examination were studied. MDA, Remodeling factors, pro-inflammatory cytokines, and inflammation in lung tissue were controlled by VIP and Ac-SDKP treatment. These treatments could enhance SOD. VIP and Ac-SDKP as immuno-regulatory factors had benefit effect in treatment of COPD. The anti-inflammatory, anti-fibrosis, and anti-oxidant properties of VIP and Ac-SDKP may be effective therapy in COPD.


Subject(s)
Oligopeptides , Pulmonary Disease, Chronic Obstructive , Vasoactive Intestinal Peptide , Animals , Mice , Anti-Inflammatory Agents/pharmacology , Cytokines , Fibrosis , Inflammation , Pulmonary Disease, Chronic Obstructive/drug therapy , Superoxide Dismutase , Vasoactive Intestinal Peptide/pharmacology , Oligopeptides/pharmacology
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