The Regulation of Pyroptosis and Ferroptosis by MicroRNAs in Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are considered the most prevalent noncommunicable disease and the leading cause of death worldwide. A plethora of evidence has revealed that microRNAs (miRNAs) could control the inhibition or progression of CVDs by regulating pivotal cell processes ranging from metabolism and homeostasis to programmed cell death (PCD). Pyroptosis and ferroptosis are two major types of nonapoptotic PCDs involved in the pathogenesis of heart failure. However, no study has discussed the crosstalk between miRNAs and these two types of PCDs in the CVDs. The current review demonstrated that different types of miRNAs can regulate both ferroptosis and pyroptosis and thereby affect CVDs progression and inhibition. Altogether, the discussed content encourages further studies to confirm that mentioned pathways are suitable to be considered as novel therapeutic approaches against CVDs.

Evaluation of CD39, CD73, HIF-1α, and their related miRNAs expression in decidua of preeclampsia cases compared to healthy pregnant women.

BACKGROUND: The Preeclampsia (PE) molecular mechanisms are not fully revealed and different biological processes are involved in the pathogenesis of PE. We aimed to evaluate adenosine and hypoxia-related signaling molecules in PE patients in the current study. METHODS: Decidua tissue and peripheral blood samples were taken from 25 healthy pregnant and 25 PE women at delivery time. CD39, CD73, and Hypoxia-inducible factor-alpha (HIF-α) were evaluated in mRNA and protein level using real-time PCR and western blotting techniques, respectively. Also, miR-30a, miR-206, and miR-18a expression were evaluated by real-time PCR. At last, secretion levels of IGF and TGF-ß in the taken serum of blood samples were measured by ELISA. RESULTS: Our results revealed that Expression of CD39 is decreased in PE cases versus healthy controls at mRNA and protein levels (p = 0.0003 for both). CD73 and HIF-α showed an increased level of expression in PE patients at RNA and protein status (p = 0.0157 and p < 0.0001 for protein evaluation of CD73 and HIF-α, respectively). The miRNA-30a (p = 0.0037) and miR-206 (p = 0.0113) showed elevated expression in the decidua of the PE group. The concentration of secreted IGF-1 (p = 0.0002) and TGF-ß (p = 0.0101) in serum samples of PE cases compared to the healthy group were decreased. CONCLUSION: In conclusion, our results showed that aberrant expression of molecules that are involved in ATP catabolism and the hypoxic conditions is observed in PE cases and involved in their hypertension and inflammation could be served as PE prognosis by more confirming in comprehensive future studies. miR-206 and miR-30a play a role by regulating CD39 and CD73 as molecules that are involved in ATP catabolism as well as regulating the production of IGF-1 in the process of hypertension, which is the main feature in patients with preeclampsia. On the other hand, decreased level of miR-18a lead to upregulation of HIF-1a, and the consequence condition of hypoxia increases hypertension and inflammation in these patients.

A comprehensive evaluation of the immune system response and type-I Interferon signaling pathway in hospitalized COVID-19 patients.

BACKGROUND: The COVID-19 pandemic has become the world's main life-threatening challenge in the third decade of the twenty-first century. Numerous studies have been conducted on SARS-CoV2 virus structure and pathogenesis to find reliable treatments and vaccines. The present study aimed to evaluate the immune-phenotype and IFN-I signaling pathways of COVID-19 patients with mild and severe conditions. MATERIAL AND METHODS: A total of 100 COVID-19 patients (50 with mild and 50 with severe conditions) were enrolled in this study. The frequency of CD4 + T, CD8 + T, Th17, Treg, and B lymphocytes beside NK cells was evaluated using flow cytometry. IFN-I downstream signaling molecules, including JAK-1, TYK-2, STAT-1, and STAT-2, and Interferon regulatory factors (IRF) 3 and 7 expressions at RNA and protein status were investigated using real-time PCR and western blotting techniques, respectively. Immune levels of cytokines (e.g., IL-1ß, IL-6, IL-17, TNF-α, IL-2R, IL-10, IFN-α, and IFN-ß) and the existence of anti-IFN-α autoantibodies were evaluated via enzyme-linked immunosorbent assay (ELISA). RESULTS: Immune-phenotyping results showed a significant decrease in the absolute count of NK cells, CD4 + T, CD8 + T, and B lymphocytes in COVID-19 patients. The frequency of Th17 and Treg cells showed a remarkable increase and decrease, respectively. All signaling molecules of the IFN-I downstream pathway and IRFs (i.e., JAK-1, TYK-2, STAT-1, STAT-2, IRF-3, and IRF-7) showed very reduced expression levels in COVID-19 patients with the severe condition compared to healthy individuals at both RNA and protein levels. Of 50 patients with severe conditions, 14 had anti-IFN-α autoantibodies in sera. Meanwhile, this result was 2 and 0 for patients with mild symptoms and healthy controls, respectively. CONCLUSION: Our results indicate a positive association of the existence of anti-IFN-α autoantibodies and immune cells dysregulation with the severity of illness in COVID-19 patients. However, comprehensive studies are necessary to find out more about this context. Video abstract.

Quantitative assessment of dacryoscintigraphic images in the evaluation of epiphora.

BACKGROUND: At the present time, only visual analysis is implemented on dacryoscintigraphic images and quantitative assessments are not routinely obtained. The authors have designed a novel, simple, quantitative method for the diagnosis of sac and post-sac obstructions based on the dacryoscintigraphic images. METHOD: Fifty-nine patients with severe unilateral epiphora were included and the contralateral asymptomatic eyes were used as controls. After ocular instillation of 0.1 cc isotonic saline containing 4 MBq 99mTcO4, dynamic images were obtained for 20 minutes. Visual interpretation was done by two blinded specialists in nuclear medicine. A Time-Activity Curve (TAC) was generated for each eye and its pattern was divided to plateau type, shallow-down sloping and deep-down sloping. The excretion ratio (expressed as the percentage of drained activity) in the 2nd, 3rd, 5th, 7th, 10th, 15th and 20th minute of the study was calculated based on the following formula: (the total count in the region of interest (ROI) in the 1st minute - the total ROI count in the 2nd, 3rd, 5th, 7th, 10th, 15th or 20th minute/the total ROI count in the 1st minute) x 100. The results of the quantitative analysis were compared with the clinical symptoms, visual analysis and TAC pattern. RESULTS: At the optimal cut-off points for the 2nd, 3rd, 5th and 7th minute, the sensitivity of the prediction of obstruction was 76%, 72%, 71% and 69%, respectively. The correlation between visual interpretation and the TAC pattern was statistically significant. CONCLUSION: The quantitative evaluation of dacryoscintigraphic images would contribute greatly to achieving an easier and more objective interpretation of the scintigraphic results and also provides a reliable tool for inter-individual comparison and the follow-up of patients. As it is the first time that this innovative method has been examined clinically, it will be necessary to investigate its clinical utility in a larger series of patients.

[On-levothyroxine measurement of thyroglobulin is not a reliable test for the follow-up of patients at high risk for remnant/recurrent differentiated thyroid carcinoma].

INTRODUCTION: At present the most widely accepted tool for follow-up management of differentiated thyroid cancer (DTC) patients is serum thyroglobulin (Tg) measurement. It is not uncommon for the serum Tg level to be measured while the patient is taking thyroid hormones (on-treatment Tg measurement). The purpose of the study was to evaluate the accuracy of on-treatment measurement of serum Tg in detecting remnant/recurrent or metastatic disease in high-risk DTC patients. MATERIAL AND METHODS: We retrospectively analysed the medical records of 26 high-risk DTC patients and compared the on-treatment and off-treatment Tg levels of these patients. All patients were anti-Tg negative. Using off-treatment measurement of Tg as the gold standard, the results of on-treatment measurement of Tg in the diagnosis of remnant/recurrent disease were analysed for sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV). RESULTS: The median serum Tg level under thyroid hormone suppressive therapy (on-treatment Tg) was 16.5 ng/ml and after withdrawal of thyroid hormone suppressive therapy (off-treatment Tg) was 95.0 ng/ml (P value = 0.001). In 6 patients (23%) the on-treatment Tg level missed the recurrence of the disease. Regarding the off-treatment Tg as the gold standard, the sensitivity, specificity, PPV and NPV of the on-treatment Tg measurement were 72.7%, 100%, 100%, and 40% respectively. CONCLUSION: Normal serum Tg level without TSH-stimulation (on-treatment) is not diagnostically reliable in the follow-up of DTC patients with a high probability of residual/recurrent or metastatic disease.