Acellular pertussis vaccines (aPVs) have been developed as an alternative to whole-cell pertussis vaccines (wPVs) due to their similar efficacy but reduced reactogenicity. The aPV contains three or more immunogenic compo...Acellular pertussis vaccines (aPVs) have been developed as an alternative to whole-cell pertussis vaccines (wPVs) due to their similar efficacy but reduced reactogenicity. The aPV contains three or more immunogenic components of BP. We aimed to evaluate the immunogenicity and protective potency of an aPV vaccine produced in our laboratory consisting of pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) in mice. The aPV components were produced and purified from the supernatant and pellet of the bacterial culture. Two doses of formulated vaccine in parallel with two commercial vaccines, were administered intraperitoneally (IP) in mice at 3-week intervals. Antibody titers against aPV antigens were measured by ELISA after primary and booster vaccinations. To assess the protective efficacy, an intranasal challenge with a live pathogenic BP strain was conducted two weeks after the booster vaccination, and bacterial count (colony-forming unit, CFU) in the lungs was conducted two hours and ten days after the challenge. The results demonstrated a significant increase in antibody titers against all pertussis antigens in the serum of vaccinated groups compared to the negative control group, following both the primary and booster doses. No significant differences were observed between our formulation and the commercial vaccines. Furthermore, the CFU results showed complete eradication of infection 10 days after the challenge in all immunized groups, in contrast to the control group. Our aPV formulation, the first aPV candidate developed in Iran, exhibits immunogenicity and protective efficacy comparable to commercial vaccines. Further investigation in human subjects is warranted.
As the most common cause of bacillary dysentery or shigellosis, Shigella sonnei (S nonnei) has spread throughout the world. Invasion of the colorectal epithelial cells by this facultative intracellular bacterium occurs v...As the most common cause of bacillary dysentery or shigellosis, Shigella sonnei (S nonnei) has spread throughout the world. Invasion of the colorectal epithelial cells by this facultative intracellular bacterium occurs via various virulence factors. The increase in the resistance rate highlights the need for novel interventions, particularly increasing the urgency of the development of Shigella vaccines that may offer an effective solution. A multiepitope protein vaccine (MEPV) construct previously designed using bioinformatics tools against Shigella species, was applied in vivo in BALB/C mice. The designed vaccine construct was expressed in a bacterial host, purified, and finally confirmed by Western blot analysis. The immunogenicity of the purified MEPV was assessed against S sonnei via intranasal and subcutaneous administration routes, followed by evaluating its protective efficiency. We observed that interferon-gamma, interleukin-4, and immunoglobulin G levels were increased in all experimental groups. Therefore, The MEPV effectively protected the mice against S sonnei.
Peripheral benign lung tumors are often asymptomatic and incidentally detected on chest radiographs. Surgical intervention is recommended when feasible. Single-port thoracoscopic resection has emerged as a promising tech...Peripheral benign lung tumors are often asymptomatic and incidentally detected on chest radiographs. Surgical intervention is recommended when feasible. Single-port thoracoscopic resection has emerged as a promising technique for treating various chest diseases, including lung tumors. This study aimed to assess the clinical efficacy of single-port thoracoscopic resection for benign lung tumors and its impact on respiratory function and inflammatory factors. A total of 128 eligible patients diagnosed with benign lung tumors were randomly assigned to either the observation group (undergoing single-port thoracoscopic resection) or the control group (undergoing conventional thoracic surgery). Surgical outcomes, complications, pulmonary and respiratory function, and inflammatory factors were compared between the two groups. The observation group showed significantly lower intraoperative bleeding, shorter hospitalization time, and lower complication rates compared to the control group. Patients in the observation group exhibited higher vital capacity (VC), forced vital capacity (FVC), and total lung capacity (TLC) levels at 1/2 week and 1 month after surgery. Additionally, forced expiratory volume in one second (FEV1) and maximum ventilation volume per minute (MVV) levels were higher in the observation group post-surgery, with a lower Borg score. Levels of C-reactive protein (CRP), precalcitonin (PCT), and tumor necrosis factor (TNF-α) were lower in the observation group post-surgery. Single-port thoracoscopic resection demonstrates favorable clinical efficacy for treating benign lung tumors, reducing bleeding, and shortening hospital stays. Furthermore, it improves lung and respiratory function while reducing inflammatory factors. This technique is safe, effective, and holds promise for wider application in managing benign lung tumors.
The coronavirus disease 2019 (CVOID-19) has varied clinical manifestations including mild to severe acute respiratory symptoms. Inflammasome complex and mitochondria play an important role in initiating inflammatory resp...The coronavirus disease 2019 (CVOID-19) has varied clinical manifestations including mild to severe acute respiratory symptoms. Inflammasome complex and mitochondria play an important role in initiating inflammatory responses and could potentially be affected by this infection. To study the inflammasome and mitochondrial fission and fusion gene expression levels in COVID-19 patients, we designed this experiment. The inflammasome and mitochondrial gene expression profiles were determined by real-time polymerase chain reaction in the peripheral blood of 70 hospitalized CVOID-19 patients with mild to moderate symptoms (HOSP) and 30 ICU patients with severe symptoms (ICU) compared to 20 healthy controls (HC). The results indicated that the expression of the dynamin-related protein-1 was extremely suppressed in HOSP while it came back to the normal range in the ICU group. However, the expression of fission 1 protein had a non-significant increase in HOSP and a decrease in the ICU group. The mitofusin-1 and dominant optic atrophy genes showed high expression levels (10-fold) and (70-fold), respectively, in the HOSP group. However, mitofusin-2 significantly decreased in both groups. Although leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) and apoptosis-associated speck-like protein containing a caspase activating and recruitment domain genes dramatically increased in both groups (10 and 4-fold), other inflammasome genes declined in both groups. Finally, Nuclear factor kappa-light-chain-enhancer of activate d B cells (NF-κB) extremely decreased, and Intreleukine-1 showed high expression in ICU patients (3-fold). CVOID-19 infection suppresses the fission genes and elevates the fusion gene expression in mitochondria, and it can cause activation of the inflammasome via the NLRP3 pathway.
Mitochondrial missense mutations and pathogenic variants have been implicated in the pathogenesis of COVID-19. This study evaluated the role of mitochondrial DNA (mtDNA) mutations and changes in gene expression in the pr...Mitochondrial missense mutations and pathogenic variants have been implicated in the pathogenesis of COVID-19. This study evaluated the role of mitochondrial DNA (mtDNA) mutations and changes in gene expression in the progression of COVID-19 and their correlation with clinical characteristics. Next-generation sequencing with high throughput was used to identify mtDNA mutations in 30 COVID-19 patients compared to 20 healthy controls. The potential impact of identified mutations on protein structure and stability was predicted using bioinformatic tools. Quantitative real-time polymerase chain reaction was employed to assess the expression levels of mtDNA-encoded genes involved in oxidative phosphorylation in COVID-19 patients and healthy controls. Correlations between gene expression levels, clinical parameters, including leukocyte, lymphocyte, neutrophil, and platelet count, as well as creatinine, alanine transaminase (ALT), aspartate transaminase (AST), and blood urea nitrogen (BUN) levels, and disease severity were analyzed. We found 8 different mtDNA mutations in ND1, ND5, CO3, ATP6, and CYB genes, which were predicted to alter amino acids and decrease protein stability. Two missense unique mutations, C9555T in CO3 and A12418T in ND5 were identified and correlated with Complexes I and IV, respectively. This downregulation was correlated with age, elevated levels of leukocytes, lymphocytes, neutrophils, platelets, creatinine, ALT, AST, and BUN, as well as disease severity. These findings suggest that mtDNA mutations and altered expression of oxidative phosphorylation genes contribute to mitochondrial dysfunction in COVID-19. Targeting mitochondrial dysfunction may represent a promising therapeutic strategy for COVID-19 treatment.
Allergic rhinitis is a common childhood disease. Although various drugs have been used to treat allergic rhinitis, including nasal corticosteroids, antileukotrienes, and antihistamines, there is still controversy about t...Allergic rhinitis is a common childhood disease. Although various drugs have been used to treat allergic rhinitis, including nasal corticosteroids, antileukotrienes, and antihistamines, there is still controversy about the optimal dose and the best combination with the highest efficacy. Higher doses of antihistamines are recommended for better control of urticaria, but there is insufficient evidence regarding the efficacy of increased doses of antihistamines in allergic rhinitis. The aim of the study was to evaluate the effectiveness of different drug combinations in the treatment of children with allergic rhinitis. Sixty-four children with persistent moderate to severe allergic rhinitis were enrolled and randomly divided into 4 groups. All children received mometasone furoate nasal spray once daily. In addition to mometasone, each group received one of the following drugs or drug combinations: daily desloratadine, twice daily desloratadine, montelukast, or a combination of desloratadine and montelukast. The severity of symptoms before and after the intervention was evaluated based on the total nasal symptoms score, including sneezing, nasal congestion, nasal itching, and rhinorrhea. Sixty patients completed the study. The reduction of nasal congestion score and total nasal symptoms score in the groups receiving desloratadine twice a day and desloratadine plus montelukast was superior to the daily desloratadine group and daily montelukast groups. According to this work, the treatment of allergic rhinitis with mometasone nasal spray with desloratadine twice a day or with the combination of desloratadine and montelukast was more effective than other treatment regimens.
To assess the impact of budesonide-formoterol on pulmonary ventilation function and prognosis in patients with mild-to-moderate acute exacerbations of bronchial asthma. A retrospective analysis was conducted on clinical...To assess the impact of budesonide-formoterol on pulmonary ventilation function and prognosis in patients with mild-to-moderate acute exacerbations of bronchial asthma. A retrospective analysis was conducted on clinical data from 232 patients with acute exacerbations of bronchial asthma. These patients were divided into 2 groups based on their treatment: a control group (n=104) receiving budesonide dry powder inhalation and an observation group (n=107) receiving budesonide-formoterol dry powder inhalation. Clinical efficacy and safety indicators were compared. The results showed that the total treatment effectiveness rate in the observation group was significantly higher than that in the control group. Following treatment, the observation group exhibited significantly higher scores in the Asthma Quality of Life Questionnaire (AQLQ), as well as improved levels of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF), compared to the control group. Moreover, levels of tumor necrosis factor-alpha, interleukin-6, and C-reactive protein were significantly lower in the observation group. The incidence of adverse reactions between groups was comparable. Based on these findings, the application of budesonide-formoterol demonstrated significant effectiveness in patients with mild-to-moderate acute exacerbations of bronchial asthma. The combination therapy led to improved clinical outcomes, including enhanced pulmonary ventilation function and reduced inflammatory markers. Importantly, the safety profile of budesonide-formoterol was comparable to that of budesonide monotherapy. These results highlight the potential benefits of using budesonide-formoterol as an alternative treatment option for patients experiencing acute exacerbations of mild-to-moderate bronchial asthma.
The purpose of this study was to systematically examine the association between bronchial asthma and lung cancer. Research on the correlation between bronchial asthma and lung cancer was retrieved from the database. Lite...The purpose of this study was to systematically examine the association between bronchial asthma and lung cancer. Research on the correlation between bronchial asthma and lung cancer was retrieved from the database. Literature was screened based on inclusion and exclusion criteria, and the number of patients in the included studies was extracted and analyzed. This study used Stata statistical software version 16.0 and Cochrane Review Manager version 5.4 for meta-analysis. In our study, 19 articles were selected. Without considering other influencing factors, the risk of lung cancer in asthma patients was relative risk (RR)=1.40 (95% CI: 1.17-1.67, I2=55.7%), and after correcting for risk factors such as smoking and age, it was found that the risk of small-cell lung cancer in asthma patients was RR=2.11 (95% CI: 1.45-3.24). Asthma may increase the risk of developing lung cancer, with an even higher likelihood for small cell lung cancer.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a complex and potentially fatal hypersensitivity condition. We present a unique case report and literature review focusing on DRESS syndrome-associated myo...Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a complex and potentially fatal hypersensitivity condition. We present a unique case report and literature review focusing on DRESS syndrome-associated myocarditis resulting from reactivated viral infections in a 21-year-old female. 3 weeks after 5-day oral co-trimoxazole consumption due to acne, she developed symptoms consistent with DRESS syndrome, including a generalized maculopapular rash. Despite prednisolone treatment, the patient developed fatal fulminant myocarditis linked to HHV-6 and CMV reactivation. The patient's death highlights the importance of early recognition and careful management of DRESS syndrome, especially considering the potential viral reactivation that can lead to severe complications. Postmortem investigations revealed that viral reactivation caused myocarditis. Careful consideration must be given to corticosteroid usage in DRESS treatment, as inappropriate prescribing may promote viral reactivation and subsequent complications. While high-dose corticosteroids initiated within the first week effectively suppress HHV-6 reactivation. Conversely, low-dose or late-start high-dose corticosteroids prove ineffective in preventing HHV-6 viremia. Late- onset or low- dose corticosteroids may lead to fatal complications following the primary viral reactivation.
This study aimed to explore the underlying mechanism of nebulized dexmedetomidine (DEX) in ameliorating ventilator-induced lung injury (VILI)-induced oxidative stress in rats. Forty 7 to 8-week-old Sprague-Dawley rats at...This study aimed to explore the underlying mechanism of nebulized dexmedetomidine (DEX) in ameliorating ventilator-induced lung injury (VILI)-induced oxidative stress in rats. Forty 7 to 8-week-old Sprague-Dawley rats at the specific pathogen-free level were randomized into the control group, model group, nebulized dexmedetomidine (WH-YM) group, and dexmedetomidine intravenous infusion (JM-YM) group, each containing 10 rats. Except for the control group, rats in the other groups underwent mechanical ventilation (tidal volume, 40 mL/kg; respiratory rate, 70 breaths per minute; inspiratory-to-expiratory ratio, 1:2; fraction of inspired oxygen, 21%; positive end-expiratory pressure, 0 cmH2O). Nebulized DEX (6.3 µg/kg), and isodose intravenous DEX were given to rats of WH-YM and JM-YM groups prior to ventilation. Post 4-hour ventilation, rats were euthanized. Lung tissue wet-to-dry weight ratio, H&E staining for assessing diffuse alveolar damage (DAD), and expression levels of Nrf2 and Keap1 detected by qRT-PCR and Western blot were compared. Inflammatory markers TNF-α, IL-2, and IL-6, and oxidative stress indices malondialdehyde (MDA) and superoxide dismutase (SOD), were quantified in lung tissues and serum samples using commercial kits. Rats in the WH-YM and JM-YM groups demonstrated significant ameliorations in the wet-to-dry weight ratio and DAD score, decreased Keap1, TNF-α, IL-2, and IL-6 levels in lung tissues and serum samples, but increased Nrf2 and SOD level than those of controls. These changes were more pronounced in the WH-YM group than in the JM-YM group. DEX effectively alleviates VILI-induced oxidative stress and inflammation via the Keap1-Nrf2-ARE signaling pathway., especially in the nebulized administration.
Today, camel milk consumption in the Middle East is trendy because it is believed that it reduces the risk of cancer. Recently, studies have discovered that most of milk's beneficial effects are because of its nanopartic...Today, camel milk consumption in the Middle East is trendy because it is believed that it reduces the risk of cancer. Recently, studies have discovered that most of milk's beneficial effects are because of its nanoparticles, especially exosomes. The objective of the present research was to investigate the anti-cancer effects of camel milk exosomes (CMEXOs) in the murine colorectal cancer cell line (CT-26). Our findings verified the existence of exosomes measuring approximately 114.1±3.4 nm in diameter. Through MTT and migration assays, we established that CMEXOs exhibit dose-dependent anti-proliferative and anti-migration effects on the CT-26 cell line. Furthermore, our study showed that treatment with CMEXOs led to a reduction in TNF-α and IL-6 gene expression in CT-26 cells. While additional in vivo studies are required, our data demonstrate that CMEXOs have anti-proliferative and anti-migration effects on CT-26, possibly by influencing crucial genes within the inflammation pathway.
The protective impacts of physical activity against inflammatory and oxidative stress conditions have been demonstrated. In this study, the impacts of moderate-intensity exercise on oxidative stress-associated factors an...The protective impacts of physical activity against inflammatory and oxidative stress conditions have been demonstrated. In this study, the impacts of moderate-intensity exercise on oxidative stress-associated factors and proinflammatory cytokines levels as well as the count of white blood cells (WBC) were assessed in a lipopolysaccharide (LPS)-triggered model of inflammation. Wistar rats were randomized into these groups (8 rats in each): (1) control; (2) LPS; (3) moderate exercise (EX); and (4) moderate exercise + LPS (EX+LPS). Exercise groups were trained for 8 weeks (30 min, 6 days/week) at 15 m/min speed. During the final week of the experiment, 1 mg/kg/day of intraperitoneal LPS was administered for 5 days. On day 56, from the rats' hearts, peripheral blood was taken for biochemical evaluation. LPS enhanced serum levels of C-reactive protein (CRP), interleukin (IL)- 1β, tumor necrosis factor-α (TNF-α), metabolites of nitric oxide, and malondialdehyde (MDA), as well as the counts of total WBC, monocytes, neutrophils, and eosinophils, but decreased serum levels of thiol as well as superoxide dismutase (SOD) and catalase (CAT) activity versus the control rats. Moderate exercise reduced the levels of thiol, CAT, and SOD, but increased TNF-α level, and total WBC, neutrophils, eosinophils, and monocytes counts versus the control group. In the EX+LPS group, moderate exercise decreased cell counts and diminished MDA, TNF-α, IL-1β, and CRP levels, while increasing thiol level, CAT, and SOD versus the LPS group. In our study, exercise preconditioning reduced inflammation induced by LPS by ameliorating inflammatory cytokine levels, WBC counts, and oxidative damage, while improving antioxidant defenses.
Rheumatoid arthritis (RA) is a type of autoimmune disease that results in immune disorder and excessive inflammatory response due to a reduction of self-tolerance. Invariant natural killer T (iNKT) cells can effectively...Rheumatoid arthritis (RA) is a type of autoimmune disease that results in immune disorder and excessive inflammatory response due to a reduction of self-tolerance. Invariant natural killer T (iNKT) cells can effectively alleviate clinical symptoms and hyper-inflammation in RA, but their mechanism of action is not well-defined. This study aims to investigate the mechanism of iNKT cell therapy for RA. We established a DBA/1 mouse model for RA and treated it with specific iNKT cells. A cytometric bead array was used to measure the amounts of cytokines in the serum. Flow cytometry was then employed to identify different subsets of helper T cells (Th), the frequency of conventional dendritic cells (cDC), the expression of CD80, CD86, programmed cell death ligand 1 (PD-L1), and PD-L2 on cDC surfaces, and associated pathway proteins. iNKT cell treatment reduced Th1/Th2 and Th17/ regulatory T (Treg) cell ratios while increasing interleukin-4 (IL-4) and IL-10. It enhanced the generation of immature cDCs, and it upregulated the level of PD-L2 by stimulating the signal transducer and activator of transcription 3 (STAT3) signaling pathway. Meanwhile, it activated the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and inhibited the nuclear factor kappa B (NF-κB) pathway. According to our findings, iNKT cell treatment increased the expression of phosphates STAT3 in lymph node cDC, causing them to upregulate PD-L2 molecules. While activating the ERK1/2 pathway and inhibiting the NF-κB pathway, tolerogenic cDC was produced, restoring immune homeostasis and correcting excessive inflammation. These results deliver new insights into the treatment of RA by iNKT cells.
Mesenchymal stem cells (MSCs) are a potential cell therapy candidate for autoimmune and inflammatory diseases due to their multilineage capacity and immune modulating function. MSCs exert immunomodulatory effects on targ...Mesenchymal stem cells (MSCs) are a potential cell therapy candidate for autoimmune and inflammatory diseases due to their multilineage capacity and immune modulating function. MSCs exert immunomodulatory effects on target cells through the secretion of exosomes. Inflammatory conditions such as Toll-like receptors (TLRs) engagement can change the biological functions and immunomodulatory activities of MSCs and the contents of exosomes derived from MSCs are changed. Regulatory T-cells (Treg) are crucial for maintaining immune cell homeostasis and self-tolerance. Our study aimed to investigate the impact of isolated exosomes from hWJ-MSCs that were treated with Poly (I:C) on regulatory CD4 CD25 Foxp3 T-cells. MSCs were harvested from human umbilical cord Wharton's Jelly by explant method. Stem cells were treated by Polyinosinic-polycytidylic acid sodium salt (Poly (I:C)) for 48 hours. Exosomes were extracted from supernatant of cells and Scanning electron microscopy (SEM) and Dynamic light scattering (DLS) were performed for them. Peripheral blood mononuclear cells (PBMCs) isolated from the healthy donors were stimulated with PHA (Phytohemagglutinin) and co-cultured with Poly (I:C) treated hWJ-MSCs derived exosome and untreated hWJ-MSCs derived exosome or without hWJ-MSCs-derived exosome for 6 days. Then, frequency of CD4+CD25+ Foxp3+ regulatory T cells was measured by flow cytometry. Our results showed that exosomes isolated from Poly (I:C) treated hWJ-MSCs significantly increased frequency of CD4+CD25+ Foxp3+ regulatory T cells compared to the untreated hWJ-MSCs derived exosome group and control group. Stimulation by TLR3 improved the anti-inflammatory features of exosomes that were derived from hWJ-MSCs by increasing the frequency of Treg cells.
Reactivation of Polyomavirus BK (BKPyV) is related to reduction of T cells response in kidney transplant recipients (KTRs). Here, we examined the differentiation of CD4+ T cells subsets in response to BKPyV KTRs, using t...Reactivation of Polyomavirus BK (BKPyV) is related to reduction of T cells response in kidney transplant recipients (KTRs). Here, we examined the differentiation of CD4+ T cells subsets in response to BKPyV KTRs, using the BKPyV VP1 (viral capsid protein 1) as a stimulator. We categorized our samples into three distinct groups: 1. Reactive BKPyV (BKPyV+), 2. non-reactive (BKPyV-) KTRs and 3. Healthy controls. BKPyV- KTRs and healthy controls stimulated with VP1 and BKPyV+ unstimulated with VP1. The human CD4+ T cells was stimulation with VP1-Ag. The proportion of CD4+ T lymphocytes and their various subsets, including naive T cells, central memory T cells (TCM), and effector memory T cells (TEM) was measured using flowcytometry. BKPyV- KTRs VP1+ indicated significantly lower TCM CD4+ T cells in contrast with both BKPyV+ KTRs VP1-, and healthy controls VP1+. This indicates that VP1 stimulation may reduce TCM cell levels in these patients. The percentage of TEM in the BKPyV- KTRs VP1+ group was significantly less prevalent than the BKPyV+ KTRs VP1- group. The percentage of TEM cells in BKPyV+ KTRs VP1- was significantly lower than the healthy controls VP1+. Stimulation with VP1 protein significantly increased the frequency of cytotoxic CD4+ T cells in BKPyV- KTRs VP1+ compared to BKPyV+ KTRs VP1-. The present research has shown that the VP1 stimulation of CD4+ T cells can induce cytotoxic CD4+ T cells responses that may help overcome BKPyV infection in KTRs. However, VP1 stimulation may also differentially affect TCM and TEM CD4+ T cells subsets.
V-domain Imuunoglobulin suppressor of T-cell activation (VISTA) seems a promising immune checkpoint target in cancer treatment; however, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) remains unkn...V-domain Imuunoglobulin suppressor of T-cell activation (VISTA) seems a promising immune checkpoint target in cancer treatment; however, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) remains unknown. Herein, 29 fresh PDAC tissue samples were used to evaluate the mRNA expression level of VISTA by real-time polymerase chain reaction (PCR). Besides, 40 formalin-fixed paraffin-embedded PDAC tissues were collected to evaluate VISTA protein expression by immunohistochemistry. Real-time PCR indicated that high expression of VISTA was significantly correlated with advanced stages of the cancer, based on the tumor/node/metastasis (TNM) stagingand tumor cell differentiation. Immunohistochemistry results also showed significant correlation of the elevated cytoplasmic expression of VISTA with advanced TNM stages, older age of the patients and was a worsening indicator, regarding the disease-specific survival. In conclusion, we found that the expression levels of VISTA can be a potential prognostic biomarker in PDAC patients and its elevated levels are correlated with poor prognostic outcomes.
Chronic rhinosinusitis whit nasal polyps (CRSwNP) is the most common comorbid disease accompanying asthma. Omalizumab is a recombinant anti-immunoglobulin (Ig) E antibody, and studies suggest that omalizumab may also aff...Chronic rhinosinusitis whit nasal polyps (CRSwNP) is the most common comorbid disease accompanying asthma. Omalizumab is a recombinant anti-immunoglobulin (Ig) E antibody, and studies suggest that omalizumab may also affect CRSwNP regardless of asthma. We aimed to assess the effect of omalizumab treatment on CRSwNP accompanying severe allergic asthma (SAA) patients. Clinical data including spirometry measurements, serum/nasal secretion biomarker levels were collected. NP scores and CRS scores (Lund-Mancay [LM] scores) were also recorded before omalizumab treatment, as well as at the 4th and 12th months of omalizumab treatment. Twenty-one patients with both CRSwNP and SAA who underwent omalizumab therapy were assessed. There was a significant difference among forced expiratory volume (FEV1), ACT scores, NP scores, LM scores, serum IgE, and blood eosinophil levels of the patients before omalizumab therapy at the 4th and 12th months of omalizumab treatment. A significant negative correlation was observed between ∆FEV1 and ∆NP scores (r=-0.485), between ∆ACT and ∆NP scores (r=-0.469), and ∆ACT and ∆LM scores (r=-0.436). When we grouped the patients who benefited from 1 year of omalizumab therapy and those who did not in terms of NP, there was no difference between the two groups related to local eosinophil and local IgE levels in the nasal polyp biopsy. Omalizumab treatment is effective for asthma and CRSwNP in patients with CRSwNP accompanied by SAA. Improvement in asthma is associated with improvement in CRSwNP. The efficacy of omalizumab on NP in patients with CRSwNP accompanied by SAA is independent of local IgE and eosinophil counts.
Graft-versus-host disease (GvHD), a frequent and severe complication following allogeneic hematopoietic stem cell transplantation, presents substantial morbidity and mortality risks. The crucial role of histopathological...Graft-versus-host disease (GvHD), a frequent and severe complication following allogeneic hematopoietic stem cell transplantation, presents substantial morbidity and mortality risks. The crucial role of histopathological examination in diagnosing and grading GvHD, particularly within animal models, is pivotal for elucidating disease mechanisms and assessing emerging therapies. This systematic review aims to critically evaluate the various grading systems for GvHD in animal models, emphasizing histopathological characteristics. In this endeavor, we meticulously examined original research articles sourced from PubMed, Scopus, Web of Science, and Google Scholar. Our findings reveal a diverse array of grading systems, each differing in the tissues examined, criteria evaluated, severity scoring scales, and the granularity of the information provided. Predominantly, skin, liver, and gut tissues are assessed, though some systems also incorporate lung and thymus evaluations. This review will delve into the alignment between clinical and histological grading in animal models of GvHD, also casting light on prospective advancements and the impact of technological progress. In conclusion, our analysis underscores the imperative need for uniform criteria and consistent application of grading systems. Such standardization is essential to foster comparability across studies and enhance the translation of preclinical discoveries into clinical applications.
The static charge on the plastic body of spacers attracts drug aerosols, reducing the drug available for inhalation from plastic spacers. Some instructions exist to decrease the electric charge on plastic spacers, such a...The static charge on the plastic body of spacers attracts drug aerosols, reducing the drug available for inhalation from plastic spacers. Some instructions exist to decrease the electric charge on plastic spacers, such as priming them with salbutamol (20 puffs) before use. This study investigates whether priming plastic spacer devices with this method can improve the bronchodilator test result. This study included children with stable mild to moderate asthma. All subjects underwent two pulmonary function tests to evaluate their bronchodilator response on separate days at 24-48 hours intervals. On each day, spirometry was performed at the baseline and 15 min after inhalation of four puffs of salbutamol (100 μg/puff) through either a primed or a new spacer. The change in forced expiratory volume in the first second (FEV1) after inhaling salbutamol was the primary outcome measure. When the patients used a new spacer, the mean baseline FEV1 (% predicted) and FEV1/FVC (forced vital capacity) were 89.56±11.95 and 86.17±6.87, respectively. However, the mean increase in FEV1 from the baseline was 10.87±8.99 in this group. On the other hand, with the primed spacer, the respective mean baseline FEV1 and FEV1/FVC values were 89.41±12.14 and 85.49±6.76, while it increased by 12.1±11.01 after salbutamol inhalation. There were no significant differences between the techniques regarding the variation in FEV1 before and after bronchodilator use via a new spacer or primed spacer. Priming new plastic spacers with 20 puffs of salbutamol did not cause additional bronchodilation in asthmatic children, suggesting this practice is inefficient in clinics.
During epithelial to mesenchymal transition, the ability of cancer cells to transform and metastasize is primarily determined by N-cadherin-mediated migration and invasion. This study aimed to evaluate whether the N-cadh...During epithelial to mesenchymal transition, the ability of cancer cells to transform and metastasize is primarily determined by N-cadherin-mediated migration and invasion. This study aimed to evaluate whether the N-cadherin promoter can induce diphtheria toxin expression as a suicide gene in epithelial to mesenchymal transition (EMT)-induced cancer cells and whether this can be used as potential gene therapy. To investigate the expression of diphtheria toxin under the N-cadherin promoter, the promoter was synthesized, and was cloned upstream of diphtheria toxin in a pGL3-Basic vector. The A-549 cells was transfected by electroporation. After induction of EMT by TGF-β and hypoxia treatment, the relative expression of diphtheria toxin, mesenchymal genes such as N-cadherin and Vimentin, and epithelial genes such as E-cadherin and β-catenin were measured by real-time PCR. MTT assay was also performed to measure cytotoxicity. Finally, cell motility was assessed by the Scratch test. After induction of EMT in transfected cells, the expression of mesenchymal markers such as Vimentin and N-cadherin significantly decreased, and the expression of β-catenin increased. In addition, the MTT assay showed promising toxicity results after induction of EMT with TGF-β in transfected cells, but toxicity was less effective in hypoxia. The scratch test results also showed that cell movement was successfully prevented in EMT-transfected cells and thus confirmed EMT occlusion. Our findings indicate that by using structures containing diphtheria toxin downstream of a specific EMT promoter such as the N-cadherin promoter, the introduced toxin can kill specifically and block EMT in cancer cells.