Evaluation of three common scoring systems in COVID-19 patients: neutrophil-lymphocyte ratio (NLR), The Acute Physiology and Chronic Health Evaluation II (APACHE II), and C-reactive protein (CRP).

Background: As SARS-CoV-2 becomes a major global health, the authors aimed to predict the severity of the disease, the length of hospitalization, and the death rate of COVID-19 patients based on The Acute Physiology and Chronic Health Evaluation II (APACHE II) criteria, neutrophil-lymphocyte ratio (NLR), and C-reactive protein (CRP) levels to prioritize, and use them for special care facilities. Methods: In a retrospective study, 369 patients with COVID-19 hospitalized in the ICU from March 2021 to April 2022, were evaluated. In addition to the APACHE II score, several of laboratory factors, such as CRP and NLR, were measured. Results: The values of CRP, NLR, and APACHE II scores were significantly higher in hospitalized and intubated patients, as well as those who died 1 month and 3 months after hospital discharge than those in surviving patients. The baseline NLR levels were the strongest factor that adversely affected death in the hospital, death 1 month and 3 months after discharge, and it was able to predict death, significantly. Conclusion: CRP, NLR, and APACHE II were all linked to prognostic factors in COVID-19 patients. NLR was a better predictor of disease severity, the need for intubation, and death than the other two scoring tools.

Doxorubicin-loaded zymosan nanoparticles: Synergistic cytotoxicity and modulation of apoptosis and Wnt/ß-catenin signaling pathway in C26 colorectal cancer cells.

Zymosan is a ß-glucan isolated from Saccharomyces cerevisiae that could be employed for drug delivery. We synthesized zymosan nanoparticles and measured their structural and morphological properties using XRD, UV-Vis spectroscopy, TEM and AFM. The loading of doxorubicin (DOX) onto the nanoparticles was confirmed by FT-IR, and the DOX release was shown to be pH-dependent. The effect of these agents on C26 cell viability was evaluated by MTT tests and the expression of genes connected with the Wnt/ß-catenin pathway and apoptosis were analyzed by RT-qPCR and Western blotting. Treatments were able to suppress the proliferation of C26 cells, and the zymosan nanocarriers loaded with DOX enhanced the anti-proliferative effect of DOX in a synergistic manner. Zymosan nanoparticles were able to suppress the expression of cyclin D1, VEGF, ZEB1, and Twist mRNAs. Treatment groups upregulated the expression of caspase-8, while reducing the Bax/Bcl-2 ratio, thus promoting apoptosis. In conclusion, zymosan nanoparticles as DOX nanocarriers could provide a more targeted drug delivery through pH-responsiveness, and showed synergistic cytotoxicity by modifying Wnt/ß-catenin signaling and apoptosis.

A rare case of carotid artery injury during maggot debridement therapy for locally advanced parotid gland carcinoma.

INTRODUCTION AND IMPORTANCE: Maggot debridement therapy (MDT) is a treatment for chronic ulcers that involves using live larvae to debride the wound. CASE PRESENTATION: We report a case of serious arterial bleeding in the cervical region in a 52-year-old woman who was hospitalized in Iran for a malignant ulcer of the retro-auricular area. The patient was brought to the hospital by Emergency medical service due to severe hemorrhagic shock. CLINICAL DISCUSSION: Debridement is a commonly used method for wound management, aimed at reducing the risk of infection and removing ulcer debridement. Several techniques are available for debridement of chronic wounds, including mechanical, surgical, autolytic, and enzymatic methods, each with its own advantages and disadvantages. CONCLUSION: Maggot debridement therapy (MDT) is one of these methods that seem to be relatively safer. In this method, some larvae are used for debriding wounds in patients. It is usually used as a last resort treatment but in this case, it was used as a third line after surgery and chemoradiotherapy.

Effect of tofacitinib on clinical and laboratory findings in severe and resistant patients with COVID-19.

BACKGROUND: The efficacy and safety of a strong Janus kinase inhibitor, tofacitinib, in individuals suffering from severe coronavirus disease 2019 (Covid-19) pneumonia are not definite well. METHODS: In this non-randomized and non-blinded trial, a total of 52 Iranian patients with severe COVID-19 associated with decreased oxygen saturation, elevated C-reactive protein, and/or persistent fever were included. A total of 52 patients were included in this study. Tofacitinib was administered to 29 patients (55.8%) in addition to the standard care treatments, whereas 23 patients (44.2%) were treated with the standard of care alone (mostly antiviral agents and corticosteroids). Tofacitinib was administered at a dose of 5 mg twice daily for up to 10 days. The primary outcomes were mortality rate, oxygen saturation level, CT findings, rate of breath, heart rate, and level of consciousness. Inflammatory cytokines and blood biomarkers were considered as the secondary outcomes. RESULTS: Death from any cause through day 14 occurred in 51.7% of the tofacitinib group and 65.2% of the control group. There was no significant difference in lung radiographic findings between the intervention and control groups at the first day of the study and after the study period. However, a significant decrease was observed in the extent of lung tissue involvement in the intervention group after administration of tofacitinib. Regarding cell and blood biomarkers, a significant decrease in the CPK levels in the intervention group and Hct and ACE levels in the control group was observed after fourteen days of the study. Moreover, a significant increase in SGOT and ferritin values was detected in the control group 14 days after the beginning tofacitinib administration. Comparing control and intervention groups, there was a significant difference in hemoglobin, SGOT, LDH, ferritin, and ACE values between groups before the intervention, while after fourteen days of the study, no significant difference was found. In case of DHEAS and TSH levels, a significant decrease was seen in the intervention group compared to the control after the study period. No other significant improvement was detected in other outcomes of the tofacitinib group compared to the control. CONCLUSIONS: The administration of tofacitinib combined with corticosteroids, is not effective enough to treat severe COVID-19 patients and the use of this medication should be considered before the disease deterioration.

Non-coding RNAs and exosomal non-coding RNAs in pituitary adenoma.

Pituitary adenoma (PA) is the third most common primary intracranial tumor in terms of overall disease incidence. Although they are benign tumors, they can have a variety of clinical symptoms, but are mostly asymptomatic, which often leads to diagnosis at an advanced stage when surgical intervention is ineffective. Earlier identification of PA could reduce morbidity and allow better clinical management of the affected patients. Non-coding RNAs (ncRNAs) do not generally code for proteins, but can modulate biological processes at the post-transcriptional level through a variety of molecular mechanisms. An increased number of ncRNA expression profiles have been found in PAs. Therefore, understanding the expression patterns of different ncRNAs could be a promising method for developing non-invasive biomarkers. This review summarizes the expression patterns of dysregulated ncRNAs (microRNAs, long non-coding RNAs, and circular RNAs) involved in PA, which could one day serve as innovative biomarkers or therapeutic targets for the treatment of this neoplasia. We also discuss the potential molecular pathways by which the dysregulated ncRNAs could cause PA and affect its progression.

Serum cystatin C and inflammatory factors related to COVID-19 consequences.

BACKGROUND: Besides impaired respiratory function and immune system, COVID-19 can affect renal function from elevated blood urea nitrogen (BUN) or serum creatinine (sCr) levels to acute kidney injury (AKI) and renal failure. This study aims to investigate the relationship between Cystatin C and other inflammatory factors with the consequences of COVID-19. METHODS: A total of 125 patients with confirmed Covid-19 pneumonia were recruited in this cross-sectional study from March 2021 to May 2022 at Firoozgar educational hospital in Tehran, Iran. Lymphopenia was an absolute lymphocyte count of less than 1.5 × 109/L. AKI was identified as elevated serum Cr concentration or reduced urine output. Pulmonary consequences were evaluated. Mortality was recorded in the hospital one and three months after discharge. The effect of baseline biochemical and inflammatory factors on odds of death was examined. SPSS, version 26, was used for all analyses. P-vale less than 0.05 was considered significant. RESULTS: The highest amount of co-morbidities was attributed to COPD (31%; n = 39), dyslipidemia and hypertension (27%; n = 34 for each) and diabetes (25%; n = 31). The mean baseline cystatin C level was 1.42 ± 0.93 mg/L, baseline creatinine was 1.38 ± 0.86 mg/L, and baseline NLR was 6.17 ± 4.50. Baseline cystatin C level had a direct and highly significant linear relationship with baseline creatinine level of patients (P < 0.001; r: 0.926). ). The average score of the severity of lung involvement was 31.42 ± 10.80. There is a direct and highly significant linear relationship between baseline cystatin C level and lung involvement severity score (r = 0.890, P < 0.001). Cystatin C has a higher diagnostic power in predicting the severity of lung involvement (B = 3.88 ± 1.74, p = 0.026). The mean baseline cystatin C level in patients with AKI was 2.41 ± 1.43 mg/L and significantly higher than patients without AKI (P > 0.001). 34.4% (n = 43) of patients expired in the hospital, and the mean baseline cystatin C level of this group of patients was 1.58 ± 0.90 mg/L which was significantly higher than other patients (1.35 ± 0.94 mg/L, P = 0.002). CONCLUSION: cystatin C and other inflammatory factors such as ferritin, LDH and CRP can help the physician predict the consequences of COVID-19. Timely diagnosis of these factors can help reduce the complications of COVID-19 and better treat this disease. More studies on the consequences of COVID-19 and knowing the related factors will help treat the disease as well as possible.

Exosomal MicroRNA Profiling.

Exosomes are extracellular vesicles, which have the ability to convey various types of cargo between cells. Lately, a great amount of interest has been paid to exosomal microRNAs (miRNAs), since much evidence has suggested that the sorting of miRNAs into exosomes is not an accidental process. It has been shown that exosomal miRNAs (exo-miRNAs) are implicated in a variety of cellular processes including (but not limited to) cell migration, apoptosis, proliferation, and autophagy. Exosomes can play a role in cardiovascular diseases and can be used as diagnostic biomarkers for several diseases, especially cancer. Tremendous advances in technology have led to the development of various platforms for miRNA profiling. Each platform has its own limitations and strengths that need to be understood in order to use them properly. In the current review, we summarize some exo-miRNAs that are relevant to exo-miRNA profiling studies and describe new methods used for the measurement of miRNA profiles in different human bodily fluids.

Manifestation of Ocular Myasthenia Gravis as an Initial Symptom of Coronavirus Disease 2019: A Case Report.

For a while, coronavirus disease-2019 (COVID-19) has been a major global pandemic. It primarily affects the respiratory system but has extrapulmonary manifestations such as gastrointestinal and neurological symptoms. Data on myasthenia gravis (MG), as a complication of COVID-19, are limited. We herein report the manifestation of ocular MG as an initial symptom of COVID-19. In November 2020, a 31-year-old healthy woman was referred to Firoozgar Hospital (Tehran, Iran) with left upper eyelid ptosis and diplopia as well as general weakness, myalgia, fever, and nasal congestion for four days prior to admission. Although the acetylcholine receptor antibody in her serum was negative, increased jitter in several muscles led to the diagnosis of ocular MG. Nasal swab reverse transcription-polymerase chain reaction (RT-PCR) assay tested positive for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Computed tomography (CT) scan of the chest revealed bilateral ground-glass opacities and some foci of consolidation formation, but the thymus was normal. The patient was successfully treated with remdesivir and dexamethasone. The patient was eventually discharged in good condition and with improved neurological symptoms. A limited number of studies have suggested a possible association between MG and COVID-19. Therefore, further data are required to substantiate the proposed association. Clinicians should be aware of ocular MG during the COVID-19 pandemic to better diagnose and manage patients with SARS-CoV-2 infection.

Microfluidics for detection of exosomes and microRNAs in cancer: State of the art.

Exosomes are small extracellular vesicles with sizes ranging from 30-150 nanometers that contain proteins, lipids, mRNAs, microRNAs, and double-stranded DNA derived from the cells of origin. Exosomes can be taken up by target cells, acting as a means of cell-to-cell communication. The discovery of these vesicles in body fluids and their participation in cell communication has led to major breakthroughs in diagnosis, prognosis, and treatment of several conditions (e.g., cancer). However, conventional isolation and evaluation of exosomes and their microRNA content suffers from high cost, lengthy processes, difficult standardization, low purity, and poor yield. The emergence of microfluidics devices with increased efficiency in sieving, trapping, and immunological separation of small volumes could provide improved detection and monitoring of exosomes involved in cancer. Microfluidics techniques hold promise for advances in development of diagnostic and prognostic devices. This review covers ongoing research on microfluidics devices for detection of microRNAs and exosomes as biomarkers and their translation to point-of-care and clinical applications.

Potential role of gut microbiota in patients with COVID-19, its relationship with lung axis, central nervous system (CNS) axis, and improvement with probiotic therapy.

Coronavirus Disease 2019 (COVID-19) is a pandemic disease caused by a new corona virus. COVID-19 affects different people in different ways. COVID-19 could affect the gastrointestinal system via gut microbiota impairment. Gut microbiota could affect lung health through a relationship between gut and lung microbiota, which is named gut-lung axis. Gut microbiota impairment plays a role in pathogenesis of various pulmonary disease states, so GI diseases were found to be associated with respiratory diseases. Moreover, most infected people will develop mild to moderate gastrointestinal (GI) symptoms such as diarrhea, vomiting, and stomachache, which is caused by impairment in gut microbiota. Therefore, the current study aimed to review potential role of gut microbiota in patients with COVID-19, its relation with lung axis, Central Nervous System (CNS) axis and improvement with probiotic therapy. Also, this review can be a guide for potential role of gut microbiota in patients with COVID-19.

Severe Persistent Eczema in a Recipient of the Gam-COVID-Vac vaccine.

Since the beginning of the COVID-19 pandemic, efforts have been made to design safe and effective vaccines against SARS-CoV-2. Numerous vaccines have been designed and tested in limited clinical trials in various countries. Among them, the Sputnik V vaccine has shown a relatively safe profile and, to our knowledge, has no associated major side effects. We describe the case of a 40-year-old female healthcare worker who developed severe persistent eczematous lesions on the second day after she received the first dose of the Sputnik vaccine. The eczematous lesions were refractory to an antihistamine and persisted at the 1 month follow-up. Severe persistent eczematous lesions should be viewed as a potential side effect of vaccination with the Sputnik V vaccine. Moreover, a severe allergic reaction to a COVID-2019 vaccine may indicate the vaccine is ineffective in the recipient. LEARNING POINTS: Vaccination against COVID-19 may be accompanied by rare complications.Eczematous lesions can be a side effect of the Sputnik V vaccine.A severe allergic reaction to a COVID-19 vaccine may result in decreased vaccine effectiveness in the recipient.

MicroRNA let-7 and viral infections: focus on mechanisms of action.

MicroRNAs (miRNAs) are fundamental post-transcriptional modulators of several critical cellular processes, a number of which are involved in host defense mechanisms. In particular, miRNA let-7 functions as an essential regulator of the function and differentiation of both innate and adaptive immune cells. Let-7 is involved in several human diseases, including cancer and viral infections. Several viral infections have found ways to dysregulate the expression of miRNAs. Extracellular vesicles (EV) are membrane-bound lipid structures released from many types of human cells that can transport proteins, lipids, mRNAs, and miRNAs, including let-7. After their release, EVs are taken up by the recipient cells and their contents released into the cytoplasm. Let-7-loaded EVs have been suggested to affect cellular pathways and biological targets in the recipient cells, and can modulate viral replication, the host antiviral response, and the action of cancer-related viruses. In the present review, we summarize the available knowledge concerning the expression of let-7 family members, functions, target genes, and mechanistic involvement in viral pathogenesis and host defense. This may provide insight into the development of new therapeutic strategies to manage viral infections.

Spontaneous Intracerebral Hemorrhage (ICH) associated with pregnancy and SARS-CoV-2 infection: a case report.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is predominately known as a respiratory disease associated with pneumonia, acute respiratory distress syndrome and multiorgan failure. However, extra-pulmonary complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are increasingly being recognized. In this regard, some studies implied the hemostatic and vascular involvements in patients with SARS-CoV-2 infection. CASE PRESENTATION: We describe a case of spontaneous Intracerebral Hemorrhage (ICH) in a pregnant patient with COVID-19 and history of cesarean section a week before the occurrence of ICH. The patient underwent emergent craniotomy with acceptable outcome. Hemorrhagic events, including ICH, may happen during COVID-19 infection with several possible mechanisms. CONCLUSION: COVID-19 patients, especially high-risk groups, are at a risk of intracranial hemorrhage. Therefore, close follow-up must be maintained and hemorrhagic events must be kept in mind in these cases.

Non-coding RNAs and glioblastoma: Insight into their roles in metastasis.

Glioma, also known as glioblastoma multiforme (GBM), is the most prevalent and most lethal primary brain tumor in adults. Gliomas are highly invasive tumors with the highest death rate among all primary brain malignancies. Metastasis occurs as the tumor cells spread from the site of origin to another site in the brain. Metastasis is a multifactorial process, which depends on alterations in metabolism, genetic mutations, and the cancer microenvironment. During recent years, the scientific study of non-coding RNAs (ncRNAs) has led to new insight into the molecular mechanisms involved in glioma. Many studies have reported that ncRNAs play major roles in many biological procedures connected with the development and progression of glioma. Long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) are all types of ncRNAs, which are commonly dysregulated in GBM. Dysregulation of ncRNAs can facilitate the invasion and metastasis of glioma. The present review highlights some ncRNAs that have been associated with metastasis in GBM. miRNAs, circRNAs, and lncRNAs are discussed in detail with respect to their relevant signaling pathways involved in metastasis.

The role of non-coding RNAs in chemotherapy for gastrointestinal cancers.

Gastrointestinal (GI) cancers, including colorectal, gastric, hepatic, esophageal, and pancreatic tumors, are responsible for large numbers of deaths around the world. Chemotherapy is the most common approach used to treat advanced GI cancer. However, chemoresistance has emerged as a critical challenge that prevents successful tumor elimination, leading to metastasis and recurrence. Chemoresistance mechanisms are complex, and many factors and pathways are involved. Among these factors, non-coding RNAs (ncRNAs) are critical regulators of GI tumor development and subsequently can induce resistance to chemotherapy. This occurs because ncRNAs can target multiple signaling pathways, affect downstream genes, and modulate proliferation, apoptosis, tumor cell migration, and autophagy. ncRNAs can also induce cancer stem cell features and affect the epithelial-mesenchymal transition. Thus, ncRNAs could possibly act as new targets in chemotherapy combinations to treat GI cancer and to predict treatment response.

Roles of Non-coding RNAs and Angiogenesis in Glioblastoma.

One of the significant hallmarks of cancer is angiogenesis. It has a crucial function in tumor development and metastasis. Thus, angiogenesis has become one of the most exciting targets for drug development in cancer treatment. Here we discuss the regulatory effects on angiogenesis in glioblastoma (GBM) of non-coding RNAs (ncRNAs), including long ncRNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA). These ncRNAs may function in trans or cis forms and modify gene transcription by various mechanisms, including epigenetics. NcRNAs may also serve as crucial regulators of angiogenesis-inducing molecules. These molecules include, metalloproteinases, cytokines, several growth factors (platelet-derived growth factor, vascular endothelial growth factor, fibroblast growth factor, hypoxia-inducible factor-1, and epidermal growth factor), phosphoinositide 3-kinase, mitogen-activated protein kinase, and transforming growth factor signaling pathways.

The Prevalence of Asthma among Iranian Children and Adolescent: A Systematic Review and Meta-Analysis.

BACKGROUND: Asthma is an important reason for hospitalization in children aged under five years. Information about the current status of asthma in Iranian children can help the Iranian health sector plan carefully and prevent asthma incidence by educating the families. The present systematic review and meta-analysis is aimed at estimating asthma prevalence in Iranian children and adolescents. METHOD: Data were found using keywords such as prevalence, epidemiology, asthma, adolescent, children, pediatrics, Iran in Web of Science, Scopus, PubMed, Cochrane, and Embase databases. Three national databases, including Magiran, Barakat Pharmed Co (Iran medex), and Scientific Information Databank (SID) were searched until 1 October 2020. Cross-sectional and original studies were included in the study, and then, quality assessment was done using the National Institutes of Health's Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. A pooled estimated prevalence of asthma was calculated using Der Simonian-Laird random model. Egger's test was used to evaluate publication bias. The data were analyzed using the STATA software version 16. RESULTS: 30 studies were selected and investigated. The prevalence of asthma in children and adolescents was 6% and 8%, and the prevalence in boys and girls was 9% and 8%, respectively. Among the asthma symptoms, wheezing had the most prevalence (17% in children and 19% in adolescents) and sleep disturbance had the lowest prevalence (6% in children and 6% in adolescents). CONCLUSION: The prevalence of asthma in Iranian children and adolescents is lower than in the world. Existing strategies should be pursued followed. Also, guidelines for asthma control and prevention should be considered in the future.

Oncogenic viruses and chemoresistance: What do we know?

Chemoresistance is often referred to as a major leading reason for cancer therapy failure, causing cancer relapse and further metastasis. As a result, an urgent need has been raised to reach a full comprehension of chemoresistance-associated molecular pathways, thereby designing new therapy methods. Many of metastatic tumor masses are found to be related with a viral cause. Although combined therapy is perceived as the model role therapy in such cases, chemoresistant features, which is more common in viral carcinogenesis, often get into way of this kind of therapy, minimizing the chance of survival. Some investigations indicate that the infecting virus dominates other leading factors, i.e., genetic alternations and tumor microenvironment, in development of cancer cell chemoresistance. Herein, we have gathered the available evidence on the mechanisms under which oncogenic viruses cause drug-resistance in chemotherapy.

Plant-based vaccines and cancer therapy: Where are we now and where are we going?

Therapeutic vaccines are an effective approach in cancer therapy for treating the disease at later stages. The Food and Drug Administration (FDA) recently approved the first therapeutic cancer vaccine, and further studies are ongoing in clinical trials. These are expected to result in the future development of vaccines with relatively improved efficacy. Several vaccination approaches are being studied in pre-clinical and clinical trials, including the generation of anti-cancer vaccines by plant expression systems.This approach has advantages, such as high safety and low costs, especially for the synthesis of recombinant proteins. Nevertheless, the development of anti-cancer vaccines in plants is faced with some technical obstacles.Herein, we summarize some vaccines that have been used in cancer therapy, with an emphasis on plant-based vaccines.

Hippocampal asymmetry and regional dispersal of nAChRs alpha4 and alpha7 subtypes in the adult rat.

To better comprehend the relationship between left/right (L/R) differences and hippocampus functions is necessary knowledge of lateral asymmetry and regional distribution. This research was design to examine hippocampal L/R asymmetry and regional distribution profile of the alpha7 and alpha4 subtypes of nicotinic acetylcholine receptors (nAChRs) in the adult rat. 10-12-week-old twenty-four male wistar rats were randomly selected. After removing the brains, immunohistochemistry, real-time PCR, and western blot methods were applied to distinguish the presence of the receptors in the hippocampus. Outcomes stated that the mentioned receptors expression profile was spatial-dependent. As, the hippocampal dispersal of alpha7 and alpha4 subtypes in the left hippocampus (LH) was remarkably maximum compare with the right hippocampus (RH) (p = 0.001, p = 0.005 respectively). Furthermore, the alpha7 optical density (OD) was not significantly different in the diverse regions in hippocampus of adult rat (p = 0.057), while the maximum OD of the alpha4 was detected in the hippocampal dentate gyrus and CA3 regions of LH (p = 0.007, p = 0.009 respectively) and the minimum OD was in the CA1 of the RH (p = 0.019). In real time PCR evaluation, there is a significantly higher expression of alpha7 and alpha4 in LH compared to RH (p = 0.043, p = 0.049 respectively), also, for western blot (p = 0.042, p = 0.030 respectively). According to present data, the alpha7 and alpha4 nAChR subtypes expression profile demonstrated lateral asymmetry, the uniform regional dispersal for alpha7 and different regional dispersal for alpha4 in the adult rat hippocampus.