Nanocurcumin modulates Th17 cell responses in moderate and severe COPD patients.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory process in the airways that results in airflow obstruction. It is mainly linked to cigarette smoke exposure. Th17 cells have a role in the pathogenesis of COPD by secreting pro-inflammatory cytokines, which cause hyperinflammation and progression of the disease. This study aimed to assess the potential therapeutic effects of nanocurcumin on the Th17 cell frequency and its responses in moderate and severe COPD patients. This study included 20 patients with severe COPD hospitalized in an intensive care unit (ICU) and 20 patients with moderate COPD. Th17 cell frequency, Th17-related factors gene expression (RAR-related orphan receptor t (RORγt), IL-17, IL-21, IL-23, and granulocyte-macrophage colony-stimulating factor), and serum levels of Th17-related cytokines were assessed before and after treatment in both placebo and nanocurcumin-treated groups using flow cytometry, real-time PCR, and ELISA, respectively. According to our findings, in moderate and severe nanocurcumin-treated COPD patients, there was a substantial reduction in the frequency of Th17 cells, mRNA expression, and cytokines secretion level of Th17-related factors compared to the placebo group. Furthermore, after treatment, the metrics mentioned above were considerably lower in the nanocurcumin-treated group compared to before treatment. Nanocurcumin has been shown to decrease the number of Th17 cells and their related inflammatory cytokines in moderate and severe COPD patients. As a result, it might be used as an immune-modulatory agent to alleviate the patient's inflammatory state.

Immunomodulatory role of Nanocurcumin in COVID-19 patients with dropped natural killer cells frequency and function.

The ongoing COVID-19 pandemic is still a challenging problem in the case of infection treatment. The immunomodulatory effect of Nanocurcumin was investigated in the present study in an attempt to counterbalance the immune response and improve the patients' clinical symptoms. 60 confirmed COVID-19 patients and 60 healthy controls enrolled in the study. COVID-19 patients were divided into Nanocurcumin and placebo received groups. Due to the importance of the role of NK cells in this disease, the frequency, cytotoxicity, receptor gene expression of NK cells, and serum secretion levels of inflammatory cytokines IL-1ß, IL-6, TNF-α, as well as circulating C5a as a chemotactic factor an inflammatory mediator was evaluated by flow cytometry, real-time PCR and enzyme-linked immunosorbent assay in both experimental groups before and after the intervention. Given the role of measured factors in the progression and pathogenesis of COVID-19 disease, the results can help find appropriate treatments. The results of this study indicated that the Nanocurcumin could significantly increase the frequency and function of NK cells compared to the placebo-treated group. As an immunomodulatory agent, Nanocurcumin may be a helpful choice to improve NK cell function in COVID-19 patients and improve the clinical outcome of patients.

Chronic obstructive pulmonary disease and asthma: mesenchymal stem cells and their extracellular vesicles as potential therapeutic tools.

Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and asthma, are one of the most frequent causes of morbidity and mortality in the global. COPD is characterized by progressive loss of lung function through inflammation, apoptosis, and oxidative stress caused by chronic exposure to harmful environmental pollutants. Airway inflammation and epithelial remodeling are also two main characteristics of asthma. In spite of extensive efforts from researchers, there is still a great need for novel therapeutic approaches for treatment of these conditions. Accumulating evidence suggests the potential role of mesenchymal stem cells (MSCs) in treatment of many lung injuries due to their beneficial features including immunomodulation and tissue regeneration. Besides, the therapeutic advantages of MSCs are chiefly related to their paracrine functions such as releasing extracellular vesicles (EVs). EVs comprising exosomes and microvesicles are heterogeneous bilayer membrane structures loaded with various lipids, nucleic acids and proteins. Due to their lower immunogenicity, tumorigenicity, and easier management, EVs have appeared as favorable alternatives to stem cell therapies. Therefore, in this review, we provided an overview on the current understanding of the importance of MSCs and MSC-derived EVs from different sources reported in preclinical and clinical COPD and asthmatic models.

A Novel Mutation in TSC2 Gene: A 34-Year-Old Female with Pulmonary Lymphangioleiomyomatosis with Concomitant Hepatic Lesions.

Tuberous sclerosis complex (TSC) is an autosomal dominant disease resulting from mutation(s) in TSC1 or TSC2 genes. TSC is associated with the formation of hamartomas in the brain, heart, eyes, skin, kidneys, and lymphangioleiomyomatosis (LAM) of the lungs. LAM is almost restricted to women in reproductive age. Different mutations in TSC1 and TSC2 genes have been reported in the literature. Here, we present a female patient with TSC-LAM with a novel mutation in TSC2 gene. The patient also had multiple hepatic angiomyolipomas, which is a relatively less-reported manifestation of the disease. The impact of this mutation on the pattern of disease presentation and response to treatment is not clear yet.

Factors associated with elevated cardiac troponin levels in patients with acute pulmonary thromboembolism.

PURPOSE: We aimed to investigate the factors that are associated with increased cardiac troponin I (cTnI) leakage in the acute pulmonary embolism (PTE) setting and their alignment with patient outcome. METHODS: Adult patients with a diagnosis of PTE were enrolled in this prospective cohort study. The primary endpoint of interest was major adverse cardio-pulmonary events (MACPE), defined as the composite of in-hospital all-cause mortality, need for thrombolysis and mechanical ventilation and surgical embolectomy during index hospitalization. Multivariable regression analysis is used to assess factors associated with MACPE. RESULTS: 16.6% of 627 patients with acute PTE, had elevated serum cTnI. MACPE occurred in 56.7% of patients with positive cTnI and in 28.8% of patients with negative cTnI (p<0.001). Blood urea nitrogen (BUN) (OR 1.048; 1.001-1.096), alanine transaminase (ALT) (OR 1.007; 1.001-1.014), and neutrophil-lymphocyte ratio (NLR) (OR 0.829; 0.698-0.984) were independent predictors of elevated cTnI. Elevated cTnI increased the risk of MACPE 2.72 times (p<0.001). CONCLUSION: cTnI was an independent predictor of short-term outcome following an episode of PTE. BUN and ALT were directly and NLR was inversely associated with the leakage of cTnI and therefore, they could potentially serve as useful markers of risk assessment after PTE.

Association of ABO blood group with incidence and outcome of acute pulmonary embolism.

OBJECTIVE: Association of ABO blood type with occurrence of pulmonary embolism (PE) has been demonstrated, and association of blood type with disease mortality and morbidity has recently been reported. Presently described was a retrospective study of mortality and morbidity according to blood group. METHODS: Blood type and medical data of 230 patients with confirmed PE was abstracted from medical records. Two control groups were used for data analysis; the 1st included blood donors (Control 1), the 2nd included hospital staff born in the same region (Control 2). RESULTS: In PE patients, blood group A was the most common phenotype (46.1%), followed by blood groups O (25.2%), B (20.4%), and AB (8.2%). Among the control groups, no significant difference was found in distribution of A vs non-A (36.4% vs 36.6%, respectively) or O vs non-O (66.6% vs 66.4%, respectively) blood groups. Blood group A was significantly more prevalent than non-A in patients with PE, compared to both control groups (p=0.002 and 0.03, respectively), and blood group O was significantly less prevalent than non-O in patients with PE, compared with both control groups (p=0.009 and 0.04, respectively). No significant difference was found in PE patients regarding in-hospital and midterm (6-36 months follow-up) mortality (p=0.36 and 0.15, respectively) based on blood groups. CONCLUSION: Blood group A was significantly more common, and blood group 0 significantly less common, in patients with PE. No association was found regarding blood type and in-hospital outcome or midterm mortality.

Modification of Simplified Pulmonary Embolism Severity Index and its Prognostic Value in Patients with Acute Pulmonary Embolism.

BACKGROUND: Various risk stratification systems have been used to predict the clinical outcome of patients with pulmonary embolism (PE). In this study we present a modification of the simplified Pulmonary Embolism Severity Index (S-PESI) score and evaluate its accuracy in predicting the outcome of these patients. MATERIALS AND METHODS: Patients older than 18 years with documented PE were enrolled in this study. S-PESI was calculated in all patients. We added electrocardiographic evidence of right ventricular strain as a new criteria and replaced the O2 saturation of <90% in S-PESI score with PaO2 /PaCO2 ratio obtained from the arterial blood gas analysis as two newly modified criteria to define a modified form of S-PESI system (modified s-PESI). Patients were followed for about one year in outpatient clinics. Any deaths attributable to PE or for unknown reasons were considered as PE related. We defined Major Adverse Cardio-Pulmonary Events (MACPE) as sum of one-year mortality, need for thrombolysis and mechanical ventilation during index hospitalisation. RESULTS: Among 300 enrolled patients, in-hospital mortality occurred in 38 (12.7%) and one-year mortality in 73 (24.3%) patients. Considering a cut-off point of 3, modified s-PESI score had a lower sensitivity (49.3% vs. 89%) and higher specificity (79.4% vs. 37.7%) than S-PESI to predict one-year mortality. Area Under Curve (AUC) to predict MACPE was significantly higher for modified s-PESI (0.692 vs 0.730, P=0.012). CONCLUSION: The modified s-PESI is superior to S-PESI in predicting one-year outcome in patients with PE and can be used for more accurate risk stratification of these patients.

The predictive Value of Total Neutrophil Count and Neutrophil/Lymphocyte Ratio in Predicting In-hospital Mortality and Complications after STEMI.

INTRODUCTION: Leukocytosis, predominantly neutrophilia, has previously been described following ST elevation myocardial infarction (STEMI). The exact contribution of this phenomenon to the clinical outcome of STEMI is yet to be shown. We examined cellular inflammatory response to STEMI in the blood and its association with in-hospital mortality and/or adverse clinical events. METHODS: In this cross-sectional study, 404 patients who were admitted with the diagnosis of acute STEMI at Madani Heart Hospital from March 2010 to March 2012 were studied. The complete blood cell count (CBC) was obtained from all patientswithin12-24 hours of the onset of symptoms. Total leukocytes were counted and differential count was obtained for neutrophils, lymphocytes and neutrophil/lymphocyte ratio (NLR) were evaluated. Association of cellular response with the incidence of post-MI mortality/complications was assessed by multiple logistic regression analyses. RESULTS: In-hospital mortality and post-STEMI complication rate were 3.7% and 43.6%, respectively. Higher age (P=0.04), female gender (0.002), lower ejection fraction (P<0.001) and absolute neutrophil count (P=0.04) were predictors of mortality. Pump failure in the form of acute pulmonary edema or cardiogenic shock occurred in 35 (8.9%) of patients. Higher leukocyte (P<0.03) and neutrophil counts (P<0.03) and higher NLR (P=0.01) were predictors of failure. The frequency of ventricular tachyarrhythmias (VT/VF) at the first day was associated with higher neutrophil count (P<0.001) and higher NLR level (P<0.001). In multivariate analysis neutrophil count was an independent predictor of mortality (OR=2.94; 1.1-8.4, P=0.04), and neutrophil count [OR=1.1, CI (1.01-1.20), P=0.02], female gender [OR=2.34, CI (1.02-4.88), P=0.04] and diabetes [OR=2.52, CI (1.21-5.2), P=0.003] were independent predictors of heart failure. CONCLUSION: A single CBC analysis may help to identify STEMI patients at risk for mortality and heart failure, and total neutrophil count is the most valuable in predicting both.