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.

NK cells - Dr. Jekyll and Mr. Hyde in autoimmune rheumatic diseases.

Natural killer (NK) cells belong to innate immune system that are large granular lymphocytes differentiating from the common lymphoid progenitors. These cells were first identified by their functional response against tumor cells and virus-infected cells. That notwithstanding, NK cells are able to affect both adaptive and innate immune arms and modulate a wide range of immune cells. As a consequence, NK cells are capable of bridging between the innate and adaptive immune responses. The effector cytokines as well as direct cell-cell cytotoxicity by NK cells have been shown to be involved in the regulation of the immune responses and might participate in the etiopathogenesis of several disorders, particularly autoimmune rheumatic diseases (AIRDs), such as Ankylosing spondylitis (AS), Rheumatoid arthritis (RA), Systemic lupus erythematosus (SLE), Behcet's disease (BD), Systemic sclerosis (SSc), and psoriasis. Nonetheless, NK cells demonstrate both harmful and protective functions during autoimmune diseases pathogenesis based on the subset of NK cell as well as disease microenvironment and disease phase or genetic/environmental stimuli. Here in this review, we intend to go through the recent findings in the etiology and pathogenesis of AIRDs and discuss about their clinical potential to be utilized as targets for the sake of therapy in the context of such disorders.

The early start of hemoperfusion decreases the mortality rate among severe COVID-19 patients: A preliminary study.

BACKGROUND: Coronavirus disease-2019 (COVID-19)-related organ failure is partly related to a sepsis-like syndrome and extreme pro-inflammatory cytokine release, named cytokine storm. Therapeutic strategies that prevent the production of or remove the pro-inflammatory cytokines could potentially be an effective therapy in critically afflicted COVID-19 patients. METHODS: In this clinical trial study, from April until June 2020, 68 COVID-19 patients (35 vs. 33 controls) with severe critical symptoms, and PaO2 /FiO2 (P/F) ratio less than 200 mmHg either received a single standard therapy or a combination of standard treatment for COVID-19 combined with hemoperfusion (hemofilter, HA330 D Javfron) for 4 h, in 3 consecutive days. The length of hospital stay and mechanical ventilation, the resolution of radiologic abnormalities, and the mortality rate were defined as the primary outcomes. RESULTS: Demographic characteristics, the acute physiology, and chronic health evaluation score of both groups were similar (p > 0.05). Importantly, we noticed a significant mortality rate reduction in the perfused group compared with controls (37.1% vs. 63.6%, p = 0.02), this positive effect was stronger among those with a P/F ratio higher than 75 (mortality rate of 84.7% for P/F ratio < 75 vs. 15.4% for P/F ratio ≥ 75, p = 0.02). CONCLUSIONS: The results imply that early start of hemoperfusion could be more effective and significantly reduce the mortality rate among COVID-19 patients with critical diseases.

Etiopathogenesis of Psoriasis from Genetic Perspective: An updated Review.

Psoriasis is an organ-specific autoimmune disease characterized by the aberrant proliferation and differentiation of keratinocytes, leading to skin lesions. Abnormal immune responses mediated by T cells and dendritic cells and increased production of inflammatory cytokines have been suggested as underlying mechanisms in the pathogenesis of psoriasis. Emerging evidence suggests that there is a heritable basis for psoriatic disorders. Moreover, numerous gene variations have been associated with the disease risk, particularly those in innate and adaptive immune responses and antigen presentation pathways. Herein, this article discusses the genetic implications of psoriatic diseases' etiopathogenesis to develop novel investigative and management options.

Th17 and Treg cells function in SARS-CoV2 patients compared with healthy controls.

In the course of the coronavirus disease 2019 (COVID-19), raising and reducing the function of Th17 and Treg cells, respectively, elicit hyperinflammation and disease progression. The current study aimed to evaluate the responses of Th17 and Treg cells in COVID-19 patients compared with the control group. Forty COVID-19 intensive care unit (ICU) patients were compared with 40 healthy controls. The frequency of cells, gene expression of related factors, as well as the secretion levels of cytokines, were measured by flow cytometry, real-time polymerase chain reaction, and enzyme-linked immunosorbent assay techniques, respectively. The findings revealed a significant increase in the number of Th17 cells, the expression levels of related factors (RAR-related orphan receptor gamma [RORγt], IL-17, and IL-23), and the secretion levels of IL-17 and IL-23 cytokines in COVID-19 patients compared with controls. In contrast, patients had a remarkable reduction in the frequency of Treg cells, the expression levels of correlated factors (Forkhead box protein P3 [FoxP3], transforming growth factor-ß [TGF-ß], and IL-10), and cytokine secretion levels (TGF-ß and IL-10). The ratio of Th17/Treg cells, RORγt/FoxP3, and IL-17/IL-10 had a considerable enhancement in patients compared with the controls and also in dead patients compared with the improved cases. The findings showed that enhanced responses of Th17 cells and decreased responses of Treg cells in 2019-n-CoV patients compared with controls had a strong relationship with hyperinflammation, lung damage, and disease pathogenesis. Also, the high ratio of Th17/Treg cells and their associated factors in COVID-19-dead patients compared with improved cases indicates the critical role of inflammation in the mortality of patients.

Interleukin 4 gene polymorphism (-589C/T) and the risk of asthma: a meta-analysis and met-regression based on 55 studies.

BACKGROUND: Numerous investigations have previously evaluated the association of interleukin (IL) 4 gene polymorphisms and the risk of asthma, conferring inconsistent results. To resolve the incongruent outcomes yielded from different single studies, we conducted the most up-to-date meta-analysis of IL4 gene -589C/T (rs2243250) polymorphism and susceptibility to asthma. METHODS: A systematic literature search was performed in ISI web of science, Scopus, Medline/PubMed databases prior to September 2020, and the pooled odds ratio (OR) and their corresponding 95% CI were calculated to determine the association strength. RESULTS: Literature search led to retrieving of 49 publications (55 case-control studies) containing 9572 cases and 9881 controls. It was revealed that IL4 gene -589C/T polymorphism increased the risk of asthma across all genetic models, including dominant model (OR = 1.22), recessive model (OR = 1.17), allelic model (OR = 1.21), and TT vs. CC model (OR = 1.34), but not the CT vs. TT model. The subgroup analysis by age indicated that IL4 gene -589C/T polymorphism was significantly associated with asthma risk in both pediatrics and adults. Additionally, the subgroup analysis by ethnicity revealed significant association in Asian, American, and Europeans. Finally, subgroup analysis by East Asian and non-East Asian populations indicated significant associations. CONCLUSIONS: The current meta-analysis revealed that IL4 gene -589C/T polymorphism was a susceptibility risk in both pediatrics and adults in the whole and different ethnic groups.

Vitamin D receptor gene polymorphisms and the risk of the type 1 diabetes: a meta-regression and updated meta-analysis.

BACKGROUND: The association between the polymorphisms in the vitamin D receptor (VDR) gene and the risk of type 1 diabetes mellitus (T1DM) has been evaluated in several studies. However, the findings were inconclusive. Thus, we conducted a meta-analysis to comprehensively evaluate the effect of VDR gene polymorphisms on the risk of T1DM. METHODS: All relevant studies reporting the association between VDR gene polymorphisms and susceptibility to T1DM published up to May 2020 were identified by comprehensive systematic database search in ISI Web of Science, Scopus, and PubMed/MEDLINE. Strength of association were assessed by calculating of pooled odds ratios (ORs) and 95% confidence intervals (CIs). The methodological quality of each study was assessed according to the Newcastle-Ottawa Scale. To find the potential sources of heterogeneity, meta-regression and subgroup analysis were also performed. RESULTS: A total of 39 case-control studies were included in this meta-analysis. The results of overall population rejected any significant association between VDR gene polymorphisms and T1DM risk. However, the pooled results of subgroup analysis revealed significant negative and positive associations between FokI and BsmI polymorphisms and T1DM in Africans and Americans, respectively. CONCLUSIONS: This meta-analysis suggested a significant association between VDR gene polymorphism and T1DM susceptibility in ethnic-specific analysis.

Acute kidney injury in pregnant women following SARS-CoV-2 infection: A case report from Iran.

We reported a 33-year-old female case with novel coronavirus disease 2019 (COVID-19) accompanied by Acute tubular necrosis (ATN). She had a gestational age of 34 weeks. The patient referred to treatment clinic for COVID-19 in Imam Reza hospital of Tabriz (Iran) after having flu-like symptoms. In radiologic assessment, ground glass opacity (GGO) with consolidation was found in upper right lobe. Lopinavir/ritonavir (200mg/50mg) two tablet tow times, Ribavirin 200mg every 6 h, and Oseltamivir 75mg tow times were given for the treatment of COVID-19. The medications used for treatment of pneumonia were Meropenem, Ciprofloxacin, Vancomycin. All doses of medications were administrated by adjusted dose assuming the patient is anephric. Also, a few supplements were also given after ATN development including daily Rocaltrol and Nephrovit (as a multivitamin appropriate for patients with renal failure), Folic acid and Calcium carbonate. The patient is still under ventilator with a Fraction of inspired oxygen (FiO2) of 60% and Positive end-expiratory pressure (PEEP) of eight. SpO2 is 94% but the patient's ATN problem has been resolved. We started weaning from mechanical ventilator. The patient is conscious with full awareness to time, person and place. The maternal well-being is achieved and her neonate was discharged.

Multiple Phantom Tumor of the Lung: A Complex Appearance Resolving with Appropriate Intervention.

The term phantom tumor may be used to describe a well-demarcated opacity resulted from pleural effusion. Phantom tumors are commonly associated with congestive heart failure causing transudative pleural effusion within pulmonary fissures. The figure may bring about inaccurate invasive diagnostic interventions. We report a heavy smoker patient with multiple phantom tumors in the right lung resolved with medical management. This case report provides records for a timely management of similar patients.

Correlation between optic nerve involvement and chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major public health problem worldwide. The aim of this study was to evaluate the rate of optic neuropathy in COPD patients. METHODS: Forty patients diagnosed with COPD and 60 healthy subjects as control group enrolled. After examination by a pulmonary subspecialist, patients were ranked by Global initiative for chronic Obstructive Lung Disease (GOLD) criteria, and patients with zero grades on GOLD criteria were excluded. Visual evoked potential by checkerboard (raster background) method with a frequency of 2 Hz were done for all participants. P-values less than 0.05 were considered as significant. RESULTS: Fifty-five percent of COPD patients had visual evoked potential abnormalities. Mean P100 latency in both eyes was significantly longer in COPD patients. Average P100/N140 amplitude in both eyes were insignificantly higher in COPD. CONCLUSION: Higher P100 latency in COPD patients shows demyelinating type of optic nerve involvement; however, further investigation in this area is needed.

Laryngeal ultrasonography versus cuff leak test in predicting postextubation stridor.

INTRODUCTION: Although cuff leak test has been proposed as a simple method of predicting the occurrence of postextubation stridor, cut-off point of cuff-leak volume substantially differs between previous studies. In addition, laryngeal ultrasonography including measurement of air column width could predict postextubation stridor. The aim of the present study was to evaluate the value of laryngeal ultrasonography versus cuff leak test in predicting postextubation stridor. METHODS: In a prospective study, all patients intubated for a minimum of 24 h for acute respiratory failure, airway protection and other causes were included. Patients were evaluated for postextubation stridor and need for reintubation after extubation. The cuff leak volume was defined as a difference between expiratory tidal volumes with the cuff inflated and deflated. Laryngeal air column width was defined as the width of air passed through the vocal cords as determined by laryngeal ultrasonography. The air-column width difference was the width difference between balloon-cuff inflation and deflation. RESULTS: Forty one intubated patients with the mean age of 57.16±20.07 years were included. Postextubation stridor was observed in 4 patients (9.75%). Cuff leak test (cut off point: 249 mL) showed sensitivity and specificity of 75% and 59%, respectively. In addition, laryngeal ultrasonography (cut off point for air column width: 10.95 mm) resulted in sensitivity and specificity of 50% and 54%, respectively. Positive predictive value of both methods were <20%. CONCLUSION: Both cuff leak test and laryngeal ultrasonography have low positive predictive value and sensitivity in predicting postextubation stridor and should be used with caution in this regard.

Quantum dots: synthesis, bioapplications, and toxicity.

This review introduces quantum dots (QDs) and explores their properties, synthesis, applications, delivery systems in biology, and their toxicity. QDs are one of the first nanotechnologies to be integrated with the biological sciences and are widely anticipated to eventually find application in a number of commercial consumer and clinical products. They exhibit unique luminescence characteristics and electronic properties such as wide and continuous absorption spectra, narrow emission spectra, and high light stability. The application of QDs, as a new technology for biosystems, has been typically studied on mammalian cells. Due to the small structures of QDs, some physical properties such as optical and electron transport characteristics are quite different from those of the bulk materials.

Sensitivity and specificity of median nerve ultrasonography in diagnosis of carpal tunnel syndrome.

BACKGROUND: Although controversial, recent studies have demonstrated advantages of sonographic techniques in the diagnosis of carpal tunnel syndrome (CTS). The purpose of this study was to assess the utility of median nerve ultrasonography in the diagnosis of CTS in Iranian patients. METHODS: Ninety patents with clinically suspected CTS were studied. Based on gold standard electromyography/nerve conduction velocity studies, wrists with CTS were divided into three groups on the basis of severity of CTS, ie, mild, moderate, and severe. In addition, both sides of the wrist were examined using sonography. Transverse images of the median nerve were obtained and median nerve cross-section areas were measured at three levels, ie, immediately proximal to the carpal tunnel inlet, at the carpal tunnel inlet, and at the carpal tunnel outlet. Furthermore, flexor retinaculum thickness was evaluated. RESULTS: The mean age of the studied patients was 48.52 ± 12.17 years. Median values of the median nerve cross-section at the carpal tunnel inlet, carpal tunnel outlet, and proximal carpal tunnel significantly differed between the wrists with and without CTS (P < 0.05). Comparisons between the CTS groups (mild, moderate, and severe) and non-CTS wrists demonstrated that the median cross-sections of median nerve at the carpal tunnel inlet, carpal tunnel outlet, and inlet proximal carpal tunnel were significantly greater in the severe CTS group than in the other three groups (P < 0.05). The results showed that the median nerve cross-section at the three levels of carpal tunnel could only fairly differentiate severe CTS from other cases. CONCLUSION: The present study demonstrated that median nerve ultrasonography cannot replace the gold standard test (nerve conduction velocity) for the diagnosis of CTS because of low overall sensitivity and specificity, although it might provide useful information in some patients.

Preparation and in vitro evaluation of doxorubicin-loaded Fe3O4 magnetic nanoparticles modified with biocompatible copolymers.

BACKGROUND: Superparamagnetic iron oxide nanoparticles are attractive materials that have been widely used in medicine for drug delivery, diagnostic imaging, and therapeutic applications. In our study, superparamagnetic iron oxide nanoparticles and the anticancer drug, doxorubicin hydrochloride, were encapsulated into poly (D, L-lactic-co-glycolic acid) poly (ethylene glycol) (PLGA-PEG) nanoparticles for local treatment. The magnetic properties conferred by superparamagnetic iron oxide nanoparticles could help to maintain the nanoparticles in the joint with an external magnet. METHODS: A series of PLGA:PEG triblock copolymers were synthesized by ring-opening polymerization of D, L-lactide and glycolide with different molecular weights of polyethylene glycol (PEG(2000), PEG(3000), and PEG(4000)) as an initiator. The bulk properties of these copolymers were characterized using (1)H nuclear magnetic resonance spectroscopy, gel permeation chromatography, Fourier transform infrared spectroscopy, and differential scanning calorimetry. In addition, the resulting particles were characterized by x-ray powder diffraction, scanning electron microscopy, and vibrating sample magnetometry. RESULTS: The doxorubicin encapsulation amount was reduced for PLGA:PEG(2000) and PLGA:PEG(3000) triblock copolymers, but increased to a great extent for PLGA:PEG(4000) triblock copolymer. This is due to the increased water uptake capacity of the blended triblock copolymer, which encapsulated more doxorubicin molecules into a swollen copolymer matrix. The drug encapsulation efficiency achieved for Fe(3)O(4) magnetic nanoparticles modified with PLGA:PEG(2000), PLGA:PEG(3000), and PLGA:PEG(4000) copolymers was 69.5%, 73%, and 78%, respectively, and the release kinetics were controlled. The in vitro cytotoxicity test showed that the Fe(3)O(4)-PLGA:PEG(4000) magnetic nanoparticles had no cytotoxicity and were biocompatible. CONCLUSION: There is potential for use of these nanoparticles for biomedical application. Future work includes in vivo investigation of the targeting capability and effectiveness of these nanoparticles in the treatment of lung cancer.

Synthesis, characterization, and in vitro evaluation of novel polymer-coated magnetic nanoparticles for controlled delivery of doxorubicin.

Poly (N-isopropylacrylamide-methyl methacrylic acid, PNIPAAm-MAA)-grafted magnetic nanoparticles were synthesized using silane-coated magnetic nanoparticles as a template for radical polymerization of N-isopropylacrylamide and methacrylic acid. Properties of these nanoparticles, such as size, drug-loading efficiency, and drug release kinetics, were evaluated in vitro for targeted and controlled drug delivery. The resulting nanoparticles had a diameter of 100 nm and a doxorubicin-loading efficiency of 75%, significantly higher doxorubicin release at 40°C compared with 37°C, and pH 5.8 compared with pH 7.4, demonstrating their temperature and pH sensitivity, respectively. In addition, the particles were characterized by X-ray powder diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, and vibrating sample magnetometry. In vitro cytotoxicity testing showed that the PNIPAAm-MAA-coated magnetic nanoparticles had no cytotoxicity and were biocompatible, indicating their potential for biomedical application.