The effects of the combination therapy of chemotherapy drugs on the fluctuations of genes involved in the TLR signaling pathway in glioblastoma multiforme therapy.

One of the most lethal and aggressive types of malignancies with a high mortality rate and poor response to treatment is glioblastoma multiforme (GBM). This means that modernizing the medications used in chemotherapy, in addition to medicines licensed for use in other illnesses and chosen using a rationale process, can be beneficial in treating this illness. Meaningly, drug combination therapy with chemical or herbal originations or implanting a drug wafer in tumors to control angiogenesis is of great importance. Importantly, the primary therapeutic hurdles in GBM are the development of angiogenesis and the blood-brain barrier (BBB), which keeps medications from getting to the tumor. This malignancy can be controlled if the drug's passage through the BBB and the VEGF (vascular endothelial growth factor), which promotes angiogenesis, are inhibited. In this way, the effect of combination therapy on the genes of different main signaling pathways like TLRs may be indicated as an impressive therapeutic strategy for treating GBM. This article aims to discuss the effects of chemotherapeutic drugs on the expression of various genes and associated translational factors involved in the TLR signaling pathway.

Practical immunomodulatory landscape of glioblastoma multiforme (GBM) therapy.

Glioblastoma multiforme (GBM) is the most common harmful high-grade brain tumor with high mortality and low survival rate. Importantly, besides routine diagnostic and therapeutic methods, modern and useful practical techniques are urgently needed for this serious malignancy. Correspondingly, the translational medicine focusing on genetic and epigenetic profiles of glioblastoma, as well as the immune framework and brain microenvironment, based on these challenging findings, indicates that key clinical interventions include immunotherapy, such as immunoassay, oncolytic viral therapy, and chimeric antigen receptor T (CAR T) cell therapy, which are of great importance in both diagnosis and therapy. Relatively, vaccine therapy reflects the untapped confidence to enhance GBM outcomes. Ongoing advances in immunotherapy, which utilizes different methods to regenerate or modify the resistant body for cancer therapy, have revealed serious results with many different problems and difficulties for patients. Safe checkpoint inhibitors, adoptive cellular treatment, cellular and peptide antibodies, and other innovations give researchers an endless cluster of instruments to plan profoundly in personalized medicine and the potential for combination techniques. In this way, antibodies that block immune checkpoints, particularly those that target the program death 1 (PD-1)/PD-1 (PD-L1) ligand pathway, have improved prognosis in a wide range of diseases. However, its use in combination with chemotherapy, radiation therapy, or monotherapy is ineffective in treating GBM. The purpose of this review is to provide an up-to-date overview of the translational elements concentrating on the immunotherapeutic field of GBM alongside describing the molecular mechanism involved in GBM and related signaling pathways, presenting both historical perspectives and future directions underlying basic and clinical practice.

A Novel Case Report of Severe Aplastic Anemia with COVID Infection.

Aplastic anemia is a rare disease of the hematopoietic system. Although some viral agents have been implicated, the association between COVID-19 and aplastic anemia is unclear. In this way, several cases of aplastic anemia have been reported following infection with COVID-19. Importantly, we reported a 16-year-old girl with severe aplastic anemia with no history of disease following an Omicron infection who did not respond well to treatment despite supportive treatment and immunosuppression.

Association between neutrophil/lymphocyte ratio and disease severity in scleroderma patients.

Introduction: Systemic sclerosis is a chronic and progressive connective tissue disease with various manifestation. Inflammatory status is developed in early stages and is followed by major organs' dysfunction. Disease severity is evaluated mostly through Medsger scale. There is not any single laboratory test to evaluate disease severity, although some hematologic can reflect disease severity. In this study, we evaluated the association between hematologic indices (specially Neutrophil/Lymphocyte ratio) and Medsger score of disease severity. Materials and methods: One hundred and twenty-three patients along with the same number of healthy controls were enrolled in this study. Demographic information and past medical records were gathered in first appointment. Hematologic indices were calculated based on the laboratory findings and the association between these indices and Medsger score of disease severity was evaluated. Results: One hundred and twenty-three patients with mean disease duration of 9.54 and mean Medsger score of 7.42 were investigated in this study. Neutrophil count, erythrocyte sedimentation rate, red cell distribution width and NLR were significantly higher and mean platelets volume was significantly lower in SSc patients in comparison to controls. NLR was significantly correlated with pulmonary and cardiac involvements and Monocyte/Lymphocyte ratio was significantly correlated with the involvement of joint and tendons. We showed that NLR is a predictive factor for the severity of systemic sclerosis. We also found a cut off Value of 1.9 for NLR as a predictor for disease severity in our patients. Conclusion: Our study shows that SSc and its severity is associated with some hematologic indices like NLR, MLR, platelets and hemoglobin. These indices can also specifically predict the involvement of some organs.

Effect of vitamin B12 on the symptom severity and psychological profile of fibromyalgia patients; a prospective pre-post study.

BACKGROUND: Fibromyalgia (FM) as a prototypical nociplastic pain condition displays a difficult therapeutic situation in many cases. Given the promising data on the effect of vitamin B12 in improving pain and cognitive functions in various nociplastic pain conditions, we aimed to determine the efficacy of 1000 mcg daily dose of oral vitamin B12 on the symptom severity and psychological profile of FM patients. METHODS: This open-label, pre-post study was performed on FM patients whose diagnoses were confirmed by a rheumatologist based on the 2016 American College of Rheumatology (ACR). Patients were instructed to take a daily dose of 1000mcg vitamin B12 for fifty days. Outcome measures including the Revised Fibromyalgia Impact Questionnaire (FIQR), Hospital Anxiety and Depression Scale (HADS), 12-item Short-Form health survey (SF-12), and pain Visual Analog Scale (pain-VAS) were fulfilled by patients before and after the treatment. RESULTS: Of 30 eligible patients, 28 patients completed the study protocol. Patients were female with a mean age of 47.50 ± 8.47 years. FIQR scores in all domains improved significantly after treatment (total FIQR: 49.8 ± 21.86 vs 40.00 ± 18.36, p value < 0.01; function: 13.17 ± 7.33 vs 10.30 ± 5.84, p value: 0.01; overall: 10.32 ± 6.22 vs 8.25 ± 6.22, p value: 0.03; symptoms: 26.30 ± 10.39 vs 21.44 ± 8.58, p value < 0.01). Vitamin B12 also improved anxiety scores from 9.33 ± 4.30 to 7.70 ± 3.60, p value: 0.01. Depression, pain-VAS, and SF-12 didn't improve following the treatment. The Generalized estimating equations (GEE) analysis showed the improvement in total FIQR score is not cofounded by the improvement of anxiety and patients' baseline characteristics. CONCLUSIONS: This study showed a short course of sublingual vitamin B12, 1000 mcg daily, significantly improves the severity of FM and anxiety score. We postulate that vitamin B12 has a strong potential to consider, at least, as adjunctive therapy of FM. TRIAL REGISTRATION: The study protocol was approved by the ethics committee of Guilan University of Medical Sciences (IR.GUMS.REC.1400.197) in accordance with the World Medical Association's code of ethics (Declaration of Helsinki, revised in Brazil 2013), and registered at an ICMJE and WHO recognized registry of clinical trials ( www.irct.ir ) on 28/08/2021 (registration number: IRCT20200920048782N1).

Association of Metabolic Syndrome and Asthma Status: A Prospective Study from Guilan Province, Iran.

INTRODUCTION: Asthma is defined as a chronic inflammatory airway disease. Recent studies have shown the association between metabolic syndrome and deterioration of lung functions in patients with asthma. The aim of this study was to evaluate the relationship between metabolic syndrome and asthma status. METHODS: In this prospective cross-sectional study, 160 asthmatic patients attending Razi hospital in Guilan province were divided equally into two groups of 80 patients. The case group comprised asthmatic patient with metabolic syndrome and the control group involved asthmatic patient without metabolic syndrome. Blood pressure, height, weight, waist circumferences, fasting blood glucose and lipid profiles were measured by standard methods. Asthma severity was determined based on clinical symptoms and GINA criteria. To evaluate pulmonary function parameters, spirometry was performed for the patients. RESULTS: Pulmonary function tests including FEF, FVC and FEV1 were significantly lower in the case group compared to the control group (P < 0.05). Also, a significant negative correlation was found between waist circumference, cardiovascular risk factors (including diabetes, hypertriglyceridemia, hypertension) with spirometric indices (P < 0.05). CONCLUSION: Metabolic syndrome causes major declines of pulmonary parameters in asthma patients; thus controlling metabolic syndrome might improve symptoms of asthma.

Incidence and Prognostic Impact of WT-1 Gene Exon7 and 9 Mutations in Acute Promyelocytic Leukemia.

Background: Wilms' tumor suppressor gene 1 (WT1) gene mutation has been reported to be a prognostic factor in normal-cytogenetic acute myeloid leukemia (AML) patients. Higher rates of mutation in the WT1 gene have been reported in several tumors including normal-cytogenetic AML patients. Data regarding WT1 mutations in acute promyelocytic leukemia (APL) is very scarce. In this study, we evaluated the incidence and impact of WT1 mutation on the outcome of APL patients. Materials and Methods: A total of 92 patients diagnosed with APL were studied in three distinct groups: early mortality, relapsed, and persistent complete remission. Genomic DNA of bone marrow samples of patients was analyzed. For quantification of expression levels of the WT1 gene, real-time quantitative PCR (rqPCR) was performed by a real-time PCR system. WT1 mutation and its impact on prognosis were considered the primary endpoint of the study. Statistical analysis was performed with STATA. Results: WT1 mutation frequency was 6.25% in the early mortality group (1/16 patients), 13.16% in the relapse group (5/38 patients), and 7.89% in the persistent complete remission group (3/38 patients). 8 mutations were in exon 7 and one mutation in exon 9. WT1 mutation in the relapse group was associated with a trend toward worse disease-free survival (DFS) while overall survival (OS) was not affected by WT1 mutation in univariate analysis. Patients with no mutations in WT1 and FLT3/ITD had better overall survival and disease-free survival compared to patients with mutations in the WT1 gene or FLT3/ITD in the relapse group. Conclusion: The frequency of WT1 gene mutations does not differ significantly between patients with early mortality, relapse, and persistent complete remission. The presence of WT1 mutation is associated with higher relapse and lower survival rates in relapse group patients.

Evaluation of hematological indices among insecticides factory workers.

Insecticides are commonly used pesticides in the world. Chronic exposure to insecticides has adverse effects on various human body organs. In this study, hematological findings were assessed in workers in an insecticide manufacturing plant. Hematological parameters and clinical symptoms were recorded in 99 workers exposed to insecticides and 107 workers not exposed to them in a cross-sectional study. Assessment of the hematological results showed a higher prevalence of thrombocytosis in the exposed group than the non-exposed group (P < 0.05). Mean white blood cell (WBC) and platelet counts, anisocytosis of red blood cells (RBCs), and neutrophils to lymphocytes ratio (NLR) were significantly higher in the exposed group compared to the non-exposed group (P < 0.05). Prevalence rates of headache, itchy skin, cough, and sleep disorders were higher in the exposed group than in the non-exposed group (P < 0.05). Chronic exposure to insecticides can alter hematological parameters in the normal range. Occupational exposure to insecticides may increase WBCs, platelet count, NLR, and red cell distribution width (RDW). It can also cause thrombocytosis. Complete blood count (CBC), as an inexpensive and accessible tool, can help monitor workers' health status exposed to insecticides properly.

Incidence and Risk Factors of Post-renal Transplantation Malignancies in North of Iran, A 20-year Experience.

INTRODUCTION: The main causes of death in kidney transplant recipients are cardiovascular diseases and malignancy. This study aimed to determine the types of post-transplant malignancy, incidence, and related factors in renal transplant recipients referred to Razi Hospital in Rasht, Iran. METHODS: This retrospective cross-sectional study was conducted on 549 kidney transplant recipients between 1998 and 2018. Patient-, transplant-, and medication-related factors and pathology reports were recorded in the check list. Chi-square, T-test and Logistic Regression were used to investigate the effect of variables. Malignancy-person-year incidence rate was calculated using survival tables and Kaplan-Mayer analysis. RESULTS: 43 (7.8%) recipients had malignancies. The most common site of malignancy was the skin (53.5%). Non-Melanoma Skin Cancer (NMSC) was the most common cancer (32.6%) followed by Kaposi sarcoma (20.9%). The standardized incidence ratio (SIR) of post-transplant malignancies in renal transplant recipients was 26.9 times the malignancies in Guilan province and 21.7 times the malignancies in Iran. Cox proportional hazard models identified older age at the time of transplantation and history of azathioprine consumption seems to be associated with risk for post-transplant malignancy. CONCLUSION: The most common malignancies in these people were non-melanoma skin cancer, Kaposi sarcoma and then GI malignancies. According to the information obtained in this study, regular periodic examinations of kidney transplant recipients for early detection of malignancy is important.