Insulin-like growth factor-1 (IGF-1) levels in multiple sclerosis patients: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Multiple sclerosis (MS) is a chronic progressive autoimmune disorder of the central nervous system (CNS) that can cause inflammation, demyelination, and axon degeneration. Insulin-like growth factor-1 (IGF-1) is a single-chain polypeptide mainly synthesized in the liver and brain. IGF-1 causes neuronal and non-neuronal cell proliferation, survival, and differentiation. Therefore, it can be used in treating neuro-demyelinating diseases such as MS. The current systematic review and meta-analysis aims to compare the levels of IGF-1 in MS patients and healthy controls and also investigates IGF binding proteins (IGF-BP) and growth hormone (GH) levels between MS patients and healthy controls. METHODS: In this study, we systematically searched electronic databases of PubMed, Scopus, Web of Science (WOS), and Google Scholar, up to December 2022. Studies that measured IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and healthy controls in either blood or cerebral spinal fluid (CSF) were identified. We calculated Standardized mean differences (SMD) to compare levels of IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and controls. RESULTS: Finally, we included 11 eligible studies from 1998 to 2018. The sample size of included studies varied from 20 to 200 resulting in a total sample size of 1067 individuals, 531 MS patients, and 536 healthy controls. The mean age of the patient and control groups were 38.96 and 39.38, respectively. The average EDSS among patients was 4.56. We found that blood levels of IGF-1 (SMD = 0.20, 95% CI = -0.20 to 0.59, I2 = 82.4%, K = 8, n = 692), CSF level of IGF-1 (SMD = 0.25, 95% CI = -0.06 to 0.56, I2 = 0.0%, K = 3 n = 164) and blood levels of GH were not significantly higher in MS patients than controls (SMD = 0.08, 95% CI = -0.33 to 0.49, I2 = 77.0% K = 3, n = 421). Moreover, the blood levels of IGFBP-1 (SMD = 0.70, 95% CI = 0.01 to 1.40, I2 = 77%, K = 4, n = 255) were significantly higher in MS cases than in controls. However, the blood levels of IGFBP-2 (SMD = 0.43, 95% CI = -0.34 to 1.21, I2 = 64.2%, K = 3, n = 78) and blood levels of IGFBP-3 (SMD = 1.04, 95% CI = -0.09 to 2.17, I2 = 95.6%, K = 6, n = 443) were not significantly higher in patients than controls. CONCLUSION: Our meta-analysis revealed no significant difference in serum levels of IGF-1, GH, IGFBP-2, and IGFBP-3 between the MS group and healthy controls, except for IGFBP1. However, our systematic review showed that the studies were controversial for IGFBP-3 serum levels. Some studies found an increase in serum level of IGFBP-3 in MS patients compared to the healthy group, while others showed a decrease.

Clinical phenotypes of patients with acute stroke: a secondary analysis.

INTRODUCTION: Stroke is a leading cause of mortality worldwide and a major cause of disability having a high burden on patients, society, and caregiving systems. This study was conducted to investigate the presence of clusters of in-hospital patients with acute stroke based on demographic and clinical data. Cluster analysis reveals patterns in patient characteristics without requiring knowledge of a predefined patient category or assumptions about likely groupings within the data. METHODS: We performed a secondary analysis of open-access anonymized data from patients with acute stroke admitted to a hospital between December 2019 to June 2021. In total, 216 patients (78; 36.1% men) were included in the analytical dataset with a mean (SD) age of 60.3 (14.4). Many demographic and clinical features were included in the analysis and the Barthel Index on discharge was used for comparing the functional recovery of the identified clusters. RESULTS: Hierarchical clustering based on the principal components identified two clusters of 109 and 107 patients. The clusters were different in the Barthel Index scores on discharge with the mean (SD) of 39.3 (29.3) versus 62.6 (29.4); t (213.87) = -5.818, P <0.001, Cohen's d (95%CI) = -0.80 (-1.07, -0.52). A logistic model showed that age, systolic blood pressure, pulse rate, D-dimer blood level, low-density lipoprotein, hemoglobin, creatinine concentration, the National Institute of Health Stroke Scale value, and the Barthel Index scores on admission were significant predictors of cluster profiles (all P ≤0.029). CONCLUSION: There are two clusters in hospitalized patients with acute stroke with significantly different functional recovery. This allows prognostic grouping of hospitalized acute stroke patients for prioritization of care or resource allocation. The clusters can be recognized using easily measured demographic and clinical features.

Diverse functions of miR-328 in the carcinogenesis.

MicroRNA-328 (miR-328) is an RNA gene that is primarily associated with lung cancer, and its encoding gene is located on 16q22.1. Expression of miR-328 has been observed in lung and esophagus tissues based on RNAseq data. Although several studies have aimed at the detection of miR-328 levels in tumor tissues, there is an obvious discrepancy between the results of these studies. Even in a certain type of cancer, some studies have reported up-regulation of miR-328 in cancerous tissues versus control tissues, while others have reported its down-regulation. This discrepancy might be attributed to different stages/grades of tumor tissues or other clinical characteristics. This review article focuses on the available literature to explore the functions of miR-328 in the development of human carcinogenesis.

Clinical efficacy of endovascular treatment approach in patients with carotid cavernous fistula: A systematic review and meta-analysis.

Background and objectives: Carotid-cavernous fistulas (CCFs) represent a group of rare, abnormal arteriovenous communications between the carotid arterial system and the cavernous sinuses (CS). CCFs often produce ophthalmologic symptoms related to increased CS pressures and retrograde venous drainage of the eye. Although endovascular occlusion remains the preferred treatment for symptomatic or high-risk CCFs, most of the data for these lesions is limited to small, single-center series. As such, we performed a systematic review and meta-analysis evaluating endovascular occlusions of CCFs to determine any differences in clinical outcomes based on presentation, fistula type, and treatment paradigm. Method: A retrospective review of all studies discussing the endovascular treatment of CCFs published through March 2023 was conducted using PubMed, Scopus, Web of Science, and Embase databases. A total of 36 studies were included in the meta-analysis. Data from the selected articles were extracted and analyzed using Stata software version 14. Results: 1494 patients were included. 55.08% were female and the mean age of the cohort was 48.10 years. A total number of 1516 fistulas underwent endovascular treatment, 48.05% of which were direct and 51.95% of which were indirect. 87.17% of CCFs were secondary to a known trauma while 10.18% were spontaneous. The most common presenting symptoms were 89% exophthalmos (95% CI: 78.0-100.0; I2 = 75.7%), 84% chemosis (95% CI: 79.0-88.0; I2 = 91.6%), 79% proptosis (95% CI: 72.0-86.0; I2 = 91.8%), 75.0% bruits (95% CI: 67.0-82.0; I2 = 90.7%), 56% diplopia (95% CI: 42.0-71.0; I2 = 92.3%), 49% cranial nerve palsy (95% CI: 32.0-66.0; I2 = 95.1%), 39% visual decline (95% CI: 32.0-45.0; I2 = 71.4%), 32% tinnitus (95% CI: 6.0-58.0; I2 = 96.7%), 29% elevated intraocular pain (95% CI: 22.0-36.0; I2 = 0.0%), 31% orbital or pre-orbital pain (95% CI: 14.0-48.0; I2 = 89.9%) and 24% headache (95% CI: 13.0-34.0; I2 = 74.98%). Coils, balloons, and stents were the three most used embolization methods respectively. Immediate complete occlusion of the fistula was seen in 68% of cases and complete remission was seen in 82%. Recurrence of CCF occurred in only 35% of the patients. Cranial nerve paralysis after treatment was observed in 7% of the cases. Conclusions: Exophthalmos, Chemosis, proptosis, bruits, cranial nerve palsy, diplopia, orbital and periorbital pain, tinnitus, elevated intraocular pressure, visual decline and headache are the most common clinical manifestations of CCFs. The majority of endovascular treatments involved coiling, balloons and onyx and a high percentage of CCF patients experienced complete remission with the improvement of their clinical symptoms.

Identification of key differentially expressed genes in SARS-CoV-2 using RNA-seq analysis with a systems biology approach.

COVID-19 is associated with dysregulation of several genes and signaling pathways. Based on the importance of expression profiling in identification of the pathogenesis of COVID-19 and proposing novel therapies for this disorder, we have employed an in silico approach to find differentially expressed genes between COVID-19 patients and healthy controls and their relevance with cellular functions and signaling pathways. We obtained 630 DEmRNAs, including 486 down-regulated DEGs (such as CCL3 and RSAD2) and 144 up-regulated DEGs (such as RHO and IQCA1L), and 15 DElncRNAs, including 9 down-regulated DElncRNAs (such as PELATON and LINC01506) and 6 up-regulated DElncRNAs (such as AJUBA-DT and FALEC). The PPI network of DEGs showed the presence of a number immune-related genes such as those coding for HLA molecules and interferon regulatory factors. Taken together, these results highlight the importance of immune-related genes and pathways in the pathogenesis of COVID-19 and suggest novel targets for treatment of this disorder.

Efficacy of Hemoperfusion in Severe and Critical Cases of COVID-19.

INTRODUCTION: Uncontrolled overproduction of inflammatory mediators is predominantly observed in patients with severe COVID-19. The excessive immune response gives rise to multiple organ dysfunction. Implementing extracorporeal therapies may be useful in omitting inflammatory mediators and supporting different organ systems. We aimed to investigate the effectiveness of hemoperfusion in combination with standard therapy in critically ill COVID-19 patients. METHOD: We conducted a single-center, matched control retrospective study on patients with confirmed SARS-CoV-2 infection. Patients were treated with hemoperfusion in combination with standard therapy (hemoperfusion group) or standard treatment (matched group). Hemoperfusion or hemoperfusion and continuous renal replacement therapies were initiated in the hemoperfusion group. The patients in the matched group were matched one by one with the hemoperfusion group for age, sex, oxygen saturation (SPO2) at the admission, and the frequency of using invasive mechanical ventilation during hospitalization. Two types of hemoperfusion cartridges used in this study were Jafron© (HA330) and CytoSorb® 300. RESULT: A total of 128 COVID-19-confirmed patients were enrolled in this study; 73 patients were allotted to the matched group and 55 patients received hemoperfusion. The median SPO2 at the admission day in the control and hemoperfusion groups was 80% and 75%, respectively (p value = 0.113). The mortality rate was significantly lower in the hemoperfusion group compared to the matched group (67.3% vs. 89%; p value = 0.002). The median length of ICU stay was statistically different in studied groups (median, 12 days for hemoperfusion group vs. 8 days for the matched group; p < 0.001). The median final SPO2 was statistically higher in the hemoperfusion group than in the matched group, and the median PaCO2 was lower. CONCLUSION: Among critically ill COVID-19 patients, based on our study, the use of hemoperfusion may reduce the mortality rate and improve SPO2 and PaCO2.

A Concise Review on Dysregulation of LINC00665 in Cancers.

Long Intergenic Non-Protein Coding RNA 665 (LINC00665) is an RNA gene located on the minus strand of chromosome 19. This lncRNA acts as a competing endogenous RNA for miR-4458, miR-379-5p, miR-551b-5p, miR-3619-5p, miR-424-5p, miR-9-5p, miR-214-3p, miR-126-5p, miR-149-3p, miR-379-5p, miR-665, miR-34a-5p, miR-186-5p, miR-138-5p, miR-181c-5p, miR-98, miR-195-5p, miR-224-5p, miR-3619, miR-708, miR-101, miR-1224-5p, miR-34a-5p, and miR-142-5p. Via influencing expression of these miRNAs, it can enhance expression of a number of oncogenes. Moreover, LINC00665 can influence activity of Wnt/ß-Catenin, TGF-ß, MAPK1, NF-κB, ERK, and PI3K/AKT signaling. Function of this lncRNA has been assessed through gain-of-function tests and/or loss-of-function studies. Furthermore, diverse research groups have evaluated its expression levels in tissue samples using microarray and RT-qPCR techniques. In this manuscript, we have summarized the results of these studies and categorized them in three sections, i.e., cell line studies, animal studies, and investigations in clinical samples.

Dynamic changes in kynurenine pathway metabolites in multiple sclerosis: A systematic review.

Background: Multiple sclerosis (MS) is a debilitating neurodegenerative disorder characterized by axonal damage, demyelination, and perivascular inflammatory lesions in the white matter of the central nervous system (CNS). Kynurenine pathway (KP), which is the major route of tryptophan (TRP) metabolism, generates a variety of neurotoxic as well as neuroprotective compounds, affecting MS pathology and the severity of impairments. Alterations in KP have been described not only in MS, but also in various psychiatric and neurodegenerative diseases. The purpose of this systematic review is to investigate the previously reported dysregulation of KP and differences in its metabolites and enzymes in patients with MS compared to healthy control subjects. Method: Electronic databases of PubMed, Scopus, Cochrane Database of Systematic Reviews, and Web of Science were searched to identify studies measuring concentrations of KP metabolites and enzymes in MS patients and control subjects. The following metabolites and enzymes implicated in the KP were investigated: TRP, kynurenine (KYN), kynurenic acid (KYNA), quinolinic acid (QUIN), picolinic acid (PIC), hydroxyindoleacetic acid (HIAA), indoleamine 2,3-dioxygenase (IDO), kynurenine aminotransferase (KAT), and their related ratios. Result: Ten studies were included in our systematic review. Our review demonstrates that IDO expression is reduced in the peripheral blood mononuclear cells (PBMCs) of MS patients compared to healthy controls. Also, increased levels of QUIN and QUIN/KYNA in the serum and cerebrospinal fluid (CSF) of MS patients is observed. Differences in levels of other metabolites and enzymes of KP are also reported in some of the reviewed studies, however there are discrepancies among the included reports. Conclusion: The results of this investigation suggest a possible connection between alterations in the levels of KP metabolite or enzymes and MS. QUIN levels in CSF were higher in MS patients than in healthy controls, suggesting that QUIN may be involved in the pathogenesis of MS. The data indicate that differences in the serum/blood or CSF levels of certain KP metabolites and enzymes could potentially be used to differentiate between MS patients and control subjects.

Evaluation of vancomycin pharmacokinetics in patients with augmented renal clearances: A randomized clinical trial.

Purpose: Vancomycin is a narrow therapeutic window glycopeptide antibiotic that acts against Gram-positive bacteria. As it is renally eliminated, therapeutic drug monitoring is recommended for vancomycin, especially in case of kidney function alteration. Augmented renal clearance (ARC), defined as a creatinine clearance of more than 130 ml/min, is a risk factor for sub-therapeutic concentrations of vancomycin. This study aimed to evaluate the vancomycin pharmacokinetics following the administration of two different regimens in ARC patients. Methods: A randomized clinical trial (IRCT20180802040665N1) was conducted on patients in need of vancomycin therapy. Eight hours of urine was collected and 56 patients divided into two groups with creatinine clearance of more than 130 ml/min were included in the study. The first group received 15 mg/kg of vancomycin every 12 h and the second group 15 mg/kg every 8 h. After four doses, the peak and trough concentrations were measured from two blood samples. The primary outcome was the percentage of patients who attainted AUC more than 400. The occurrence of acute kidney injury also was evaluated after seven days. Results: The mean age of patients in the every 12 h and every 8 h groups was 44.04 ± 16.55 and 42.86 ± 11.83 years, respectively. While neurosurgical issues were the most common causes of hospitalization, central nervous infections were the most common indications for vancomycin initiation. Urinary creatinine clearance was 166.94 ± 41.32 ml/min in the every 12 h group and 171.78 ± 48.56 ml/min in the every 8 h group. 46.42% of patients in the every 12 h group and 82.14% of patients in the every 8 h group attained AUC/MIC of more than 400 mg × hr/L. None of the patients in the every 12 h group reached more than 15 mcg/ml concentration. At the 7-day follow-up, 10.7% patients in the BD group and 28.6% patients in the TDS group developed acute kidney injury (p = 0.089). Conclusion: Administration of vancomycin at a dose of 15 mg/kg every 8 h is associated with higher pharmacokinetic attainment in ARC patients. The occurrence of acute kidney injury also was not significantly higher in this therapeutic regimen. AUC/MIC monitoring is necessary in this population.

Cardiovascular Complications of COVID-19 among Pregnant Women and Their Fetuses: A Systematic Review.

BACKGROUND: COVID-19 is a viral infectious disease leading to a spectrum of clinical complications, especially cardiovascular. Evidence shows that this infection can potentially accompany a worse outcome in pregnant women. Cardiovascular complications in mothers and their fetuses are reported by previous studies. OBJECTIVE: In this systematic review, we aim to investigate the cardiovascular complications of COVID-19 during pregnancy in the mothers and fetus, according to the published literature. METHOD: We systematically searched the online databases of PubMed, Scopus, Web of Science, and Google Scholar, using relevant keywords up to April 2022. We included all observational studies reporting cardiovascular complications among COVID-19-affected pregnant women and their fetuses. RESULTS: We included 74 studies containing 47582 pregnant COVID-19 cases. Pre-eclampsia, hypertensive disorders, cardiomyopathy, heart failure, myocardial infarction, thrombosis formation, alterations in maternal-fetal Doppler patterns, and maternal and fetal arrhythmia were reported as cardiovascular complications. The highest incidences of pre-eclampsia/eclampsia among COVID-19 pregnant cases, reported by studies, were 69% and 62%, and the lowest were 0.5% and 3%. The highest and lowest incidences of fetal bradycardia were 20% and 3%, and regarding fetal tachycardia, 5.4% and 1%, respectively. CONCLUSION: SARS-CoV-2 infection during pregnancy can potentially be associated with cardiovascular complications in the mother, particularly pre-eclampsia and heart failure. Moreover, SARS-CoV-2 infection during pregnancy can potentially cause cardiovascular complications in the fetus, particularly arrhythmia.

A review on the role of LINC00467 in the carcinogenesis.

LINC00467 is an example of long intergenic non-coding RNAs whose roles in human disorders are being identified. This gene coding LINC00467 is located on chromosome 1: 211,382,736 - 211,435,570 forward strand. This lncRNA has been firstly recognized through a microarray-based lncRNA profiling as an N-Myc target in neuroblastoma cells. Further studies have shown up-regulation of LINC00467 in different cancer including those originated from brain, gastrointestinal tract, lung and breast. It acts as a molecular sponge for miR-339, miR-138-5p, miR-107, miR-133b, miR-451a, miR-485-5p, miR-7-5p, miR-485-5p, miR-339-3p, miR-200a, miR-1285-3p, miR-299-5p, miR-509-3p, miR-18a-5p, miR-9-5p and miR-20b-5p. LINC00467 can regulate activity of NF-κB, STAT1, Wnt/b-catenin, Akt and ERK1/2 signaling pathways. Accumulating evidence indicates oncogenic role of LINC00467. The current review article aims at providing an overview of LINC00467 in the carcinogenesis.

Downregulation of oxytocin-related genes in periodontitis.

Periodontitis is a common oral disorder leading to tooth loss in both developed and developing regions of the world. This multifactorial condition is related to the abnormal activity of several molecular pathways, among them are oxytocin-related pathways. In this study, we enrolled 26 patients and 28 controls and assessed the expression of four oxytocin-related genes, namely, FOS, ITPR, RCAN1, and RGS2, in circulation and affected tissues of enrolled individuals using real-time PCR. Expression of FOS was downregulated in total periodontitis tissues compared with total control tissues [ratio of mean expression (RME) = 0.23, P-value = 0.03]. Expression of FOS was also lower in total blood samples of patients compared with total controls. Expression of ITPR was downregulated in total periodontitis tissues compared with total control tissues (RME = 0.16, P-value = 0.01). Moreover, the expression of ITPR was reduced in total blood samples of patients compared with controls (RME = 0.25, P-value = 0.03). Expression of RCAN1 was downregulated in total periodontitis tissues compared with total control tissues (RME = 0.17, P-value = 0.01). However, the expression of RCAN1 was not different in blood samples of affected vs. unaffected individuals. Finally, the expression of RGS2 was lower in total periodontitis tissues compared with total control tissues (RME = 0.24, P-value = 0.01) and in total blood samples of affected individuals compared with controls (RME = 0.42, P-value = 0.05). This study provides data about the association between expressions of oxytocin-related genes and the presence of periodontitis. Future studies are needed to unravel the mechanistic links and find the correlation between expressions of these genes and the pathological stage of periodontitis.

A Comprehensive Review on Function of miR-15b-5p in Malignant and Non-Malignant Disorders.

miR-15b-5p is encoded by MIR15B gene. This gene is located on cytogenetic band 3q25.33. This miRNA participates in the pathogenesis of several cancers as well as non-malignant conditions, such as abdominal aortic aneurysm, Alzheimer's and Parkinson's diseases, cerebral ischemia reperfusion injury, coronary artery disease, dexamethasone induced steatosis, diabetic complications and doxorubicin-induced cardiotoxicity. In malignant conditions, both oncogenic and tumor suppressor impacts have been described for miR-15b-5p. Dysregulation of miR-15b-5p in clinical samples has been associated with poor outcome in different kinds of cancers. In this review, we discuss the role of miR-15b-5p in malignant and non-malignant conditions.

The Predictive Power of Near-Infrared Spectroscopy in Improving Cognitive Problems in Patients Undergoing Brain Surgeries: A Systematic Review.

One of the main objectives in neurosurgical procedures is the prevention of cerebral ischemia and hypoxia leading to secondary brain injury. Different methods for early detection of intraoperative cerebral ischemia and hypoxia have been used. Near-infrared spectroscopy (NIRS) is a simple, non-invasive method for monitoring cerebral oxygenation increasingly used today. The aim of this study was to systematically review the brain monitoring with NIRS in neurosurgery. The search process resulted in the detection of 324 articles using valid keywords on the electronic databases, including Embase, PubMed, Scopus, Web of Science, and Cochrane Library. Subsequently, the full texts of 34 studies were reviewed, and finally 11 articles (seven prospective studies, three retrospective studies, and one randomized controlled trial) published from 2005 to 2020 were identified as eligible for systematic review. Meta-analysis was not possible due to high heterogeneity in neurological and neurosurgical conditions of patients, expression of different clinical outcomes, and different standard reference tests in the studies reviewed. The results showed that NIRS is a non-invasive cerebral oximetry that provides continuous and measurable cerebral oxygenation information and can be used in a variety of clinical settings.

Therapeutic Potential of Microvesicles in Cell Therapy and Regenerative Medicine of Ocular Diseases With an Especial Focus on Mesenchymal Stem Cells-Derived Microvesicles.

These days, mesenchymal stem cells (MSCs), because of immunomodulatory and pro-angiogenic abilities, are known as inevitable factors in regenerative medicine and cell therapy in different diseases such as ocular disorder. Moreover, researchers have indicated that exosome possess an essential potential in the therapeutic application of ocular disease. MSC-derived exosome (MSC-DE) have been identified as efficient as MSCs for treatment of eye injuries due to their small size and rapid diffusion all over the eye. MSC-DEs easily transfer their ingredients such as miRNAs, proteins, and cytokines to the inner layer in the eye and increase the reconstruction of the injured area. Furthermore, MSC-DEs deliver their immunomodulatory cargos in inflamed sites and inhibit immune cell migration, resulting in improvement of autoimmune uveitis. Interestingly, therapeutic effects were shown only in animal models that received MSC-DE. In this review, we summarized the therapeutic potential of MSCs and MSC-DE in cell therapy and regenerative medicine of ocular diseases.

The Emerging Roles of the ß-Secretase BACE1 and the Long Non-coding RNA BACE1-AS in Human Diseases: A Focus on Neurodegenerative Diseases and Cancer.

The ß-Secretase (BACE1) is widely studied to be particularly involved in amyloid deposition, a process known as the pathogenic pathway in neurodegenerative diseases. Therefore, BACE1 expression is frequently reported to be upregulated in brain samples of the patients with Alzheimer's disease (AD). BACE1 expression is regulated by BACE1-AS, a long non-coding RNA (lncRNA), which is transcribed in the opposite direction to its locus. BACE1-AS positively regulates the BACE1 expression, and their expression levels are regulated in physiological processes, such as brain and vascular homeostasis, although their roles in the regulation of amyloidogenic process have been studied further. BACE1-AS dysregulation is reported consistent with BACE1 in a number of human diseases, such as AD, Parkinson's disease (PD), heart failure (HF), and mild cognitive impairment. BACE1 or less BACE1-AS inhibition has shown therapeutic potentials particularly in decreasing manifestations of amyloid-linked neurodegenerative diseases. Here, we have reviewed the role of lncRNA BACE1 and BACE1-AS in a number of human diseases focusing on neurodegenerative disorders, particularly, AD.

Correlation between Legionella pneumophila serogroups isolated from patients with ventilator-associated pneumonia and water resources: a study of four hospitals in Tehran, Iran.

Legionella pneumophila (L. pneumophila) is one of the main pathogens, causing pneumonia and respiratory tract infections, especially in patients with ventilator-associated pneumonia (VAP). This study aimed to approve the hypothesis that the serogroup distribution of L. pneumophila isolates from patients is correlated with Legionella strains in the environment. A total of 280 bronchoalveolar lavage (BAL) samples from VAP patients admitted to the intensive care unit (ICU) as well as 116 water samples from different sources in four hospitals in Tehran, Iran, were evaluated for the presence of L. pneumophila infection by culture, nested polymerase chain reaction (PCR), real-time PCR, and sequencing for genetic diversity. The molecular and culture methods found 24 (8.6%) and 5 (1.8%) samples to be positive for L. pneumophila in VAP patients, while they found 23 (19.8%) and 8 (6.9%) positive samples in water resources, respectively. The sequencing results indicated that all positive clinical samples and 14 (60.8%) environmental samples were belonged to L. pneumophila serogroup 1. Smoking, age, length of ICU stay, and duration of ventilator use had strong relationship with L. pneumophila infectivity. In conclusion, this is the first report from Iran to determine minor differences in the serogroup distribution of environmental and clinical strains. However, further studies are needed to confirm this relationship in different regions of Iran.

Signaling pathways modulated by miRNAs in breast cancer angiogenesis and new therapeutics.

MicroRNAs (miRNAs) act as oncogenes or tumor suppressors by suppressing the expression of target genes, some of which are engaged in angiogenic signaling pathways directly or indirectly. Tumor development and metastasis are dependent on angiogenesis, and it is the main reason for the poor prognosis of cancer patients. New blood vessels are formed from pre-existing vessels when angiogenesis occurs. Thus, it is essential to develop primary tumors and the spread of cancer to surrounding tissues. MicroRNAs (miRNAs) are small noncoding RNAs involved in various biological processes. They can bind to the 3'-UTR of their target genes and prevent them from expressing. MiRNAs control the activity of endothelial cells (ECs) through altering many biological pathways, which plays a key role in cancer progression and angiogenesis. Recent findings revealed that tumor-derived extracellular vesicles participated directly in the control of tumor angiogenesis by delivering miRNAs to ECs. miRNAs recently show great promise in cancer therapies to inhibit angiogenesis. In this study, we showed the miRNA-regulated signaling pathways in tumor angiogenesis with highlighting the anti-angiogenic therapy response and miRNA delivery methods that have been used to inhibit angiogenesis in both in vivo and in vitro studies.

Study of the effects of interferon ß-1a on hospitalized patients with COVID-19: SBMU Taskforce on the COVIFERON study.

Interferons are an essential part of the innate immune system and have antiviral and immunomodulatory functions. We studied the effects of interferon ß-1a on the outcomes of severe cases of coronavirus disease 2019 (COVID-19). This retrospective study was conducted on hospitalized COVID-19 patients in Loghman-Hakim hospital from February 20, 2020 to April 20, 2020, Tehran, Iran. Patients were selected from two groups, the first group received interferon ß-1a in addition to the standard treatment regimen, and the second group received standard care. The clinical progression of two groups during their hospital admission was compared. We studied a total number of 395 hospitalized COVID-19 patients. Out of this number, 111 patients (33.5%) died (31.3% of the interferon ß-1a group and 34.1% of the control group). The mortality rate indicated no statistically significant difference between groups (p-value = 0.348), however for patients who were hospitalized for more than a week, the rate of mortality was lower in the interferon ß-1a group (p-value = 0.014). The median hospital stay was statistically longer for patients treated by interferon ß-1a (p-value < 0.001). The results of this study showed that interferon ß-1a can improve the outcomes of hospitalized patients with severe COVID-19, but more adequately-powered randomized controlled trials should be conducted.

Challenges of cancer immunotherapy and chemotherapy during the COVID-19 pandemic.

People at high risk of morbidity and mortality from coronavirus disease 2019 (COVID-19), including patients dealing with malignancies and patients on immunosuppressive anticancer therapies, need to be followed carefully as the pandemic continues. Challenges in continuing cancer management and patient monitoring are of concern given the importance of timing in cancer therapy. Alternative treatment decisions and priorities are also important considerations. The efficacy and safety of various cancer treatments in patients with COVID-19 are other important considerations. In this systematic review, we summarize the potential risks and benefits of cancer treatments applied to patients with COVID-19 and malignant tumors. Using the PubMed and Scopus databases, we reviewed studies involving cancer therapy and COVID-19 to address the recent discoveries and related challenges of cancer therapy in patients with COVID-19 and cancer.