Epidemiology of malignant gliomas in Iran: first report of Iranian National Population-based Cancer Registry, 2009-2017.

OBJECTIVE: Malignant gliomas constitute the most common type of primary malignant brain tumors. Most previous studies have evaluated the epidemiology of malignant gliomas in developed countries. Hence, there is a lack of evidence in this regard from developing countries. This study is the first epidemiological report on the status of malignant glioma in Iran between 2009 and 2017. METHODS: Data from the Iranian National Population-based Cancer Registry (covering 98% of the Iranian population) on CNS tumors recorded from 2009 to 2017 were used for analysis. Age-adjusted incidence rates were calculated by sex, tumor histology, tumor site, and year of diagnosis. Trend analysis of incidence rates was also performed. Survival data were recorded and the Cox proportional hazards model was used to evaluate underlying risk factors. RESULTS: A total of 8484 patients were diagnosed with malignant glioma between 2009 and 2017 in Iran. The overall age-adjusted incidence rate of malignant gliomas over the 9-year period was 1.71 per 100,000 persons. The most common histology of malignant gliomas was glioblastoma (81.4%). A significant increase in the incidence of malignant gliomas was found between 2009 and 2012. The median overall survival was 13.0 (95% CI 12.6-13.5) months over the study period. Older age groups, higher tumor grade, male sex, the first half of the study period, and receiving no treatment were significantly associated with worse prognoses. CONCLUSIONS: This study is the latest epidemiological report on the status of malignant gliomas in Iran. Although the overall incidence rate was lower than the rates in developed countries, several findings were consistent with those in prior reports.

Calculating transmembrane voltage on the electric pulse-affected cancerous cell membrane: using molecular dynamics and finite element simulations.

CONTEXT: Electroporation is a technique that creates electrically generated pores in the cell membrane by modifying transmembrane potential. In this work, the finite element method (FEM) was used to examine the induced transmembrane voltage (ITV) of a spherical-shaped MCF-7 cell, allowing researchers to determine the stationary ITV. A greater ITV than the critical value causes permeabilization of the membrane. Furthermore, the present study shows how a specific surface conductivity can act as a stand-in for the thin layer that constitutes a cell membrane as the barrier between extracellular and intracellular environments. Additionally, the distribution of ITV on the cell membrane and its maximum value were experimentally evaluated for a range of applied electric fields. Consequently, the entire cell surface area was electroporated 66% and 68% for molecular dynamics (MD) simulations and FEM, respectively, when the external electric field of 1500 V/cm was applied to the cell suspension using the previously indicated numerical methods. Furthermore, the lipid bilayers' molecular structure was changed, which led to the development of hydrophilic holes with a radius of 1.33 nm. Applying MD and FEM yielded threshold values for transmembrane voltage of 700 and 739 mV, respectively. METHOD: Using MD simulations of palmitoyloleoyl-phosphatidylcholine (POPC), pores in cell membranes exposed to external electric fields were numerically investigated. The dependence on the electric field was estimated and developed, and the amount of the electroporated cell surface area matches the applied external electric field. To investigate more, a mathematical model based on an adaptive neuro-fuzzy inference system (ANFIS) is employed to predict the percent cell viability of cancerous cells after applying four pulses during electroporation. For MD simulations, ArgusLab, VMD, and GROMACS software packages were used. Moreover, for FEM analysis, COMSOL software package was used. Also, it is worth mentioning that for mathematical model, MATLAB software is used.

Efficacy and Safety of Vaccines After Conventional Treatments for Survival of Gliomas: A Systematic Review and Meta-Analysis.

Background: Malignant gliomas are known with poor prognosis and low rate of survival among brain tumors. Resection surgery is followed by chemotherapy and radiotherapy in treatment of gliomas which is known as the conventional treatment. However, this treatment method results in low survival rate. Vaccination has been suggested as a type of immunotherapy to increase survival rate of glioma patients. Different types of vaccines have been developed that are mainly classified in two groups including peptide vaccines and cell-based vaccines. However, there are still conflicts about which type of vaccines is more efficient for malignant glioma treatment. Methods: Phase Ⅰ/Ⅱ clinical trials which compared the efficacy and safety of various vaccines with conventional treatments were searched in databases through November 2022. Overall survival (OS) rate, progression free survival (PFS), and OS duration were used for calculation of pooled risk ratio (RR). In addition, fatigue, headache, nausea, diarrhea, and flu-like syndrome were used for evaluating the safety of vaccines therapy in glioma patients. Results: A total of twelve articles were included in the present meta-analysis. Comparison of OS rate between vaccinated groups and control groups who underwent only conventional treatments showed a significant increase in OS rate in vaccinated patients (I2 = 0%, RR = 11.17, 95% CI: 2.460-50.225). PFS rate was better in vaccinated glioma patients (I2 = 83%, RR = 2.87, 95% CI: 1.63-5.03). Assessment of safety demonstrated that skin reaction (I2 = 0.0%, RR = 3.654; 95% CI: 1.711-7.801, p-value = 0.0058) and flu-like syndrome were significantly more frequent adverse effects win vaccinated groups compared to the control group. Subgroup analysis also showed that vaccination leads to better OS duration in recurrent gliomas than primary gliomas, and in LGG than HGG (p-value = 0). On the other hand, personalized vaccines showed better OS duration than non-personalized vaccines (p-value = 0). Conclusion: Vaccination is a type of immunotherapy which shows promising efficacy in treatment of malignant glioma patients in terms of OS, PFS and duration of survival. In addition, AFTV, peptide, and dendritic cell-based vaccines are among the most efficient vaccines for gliomas. Personalized vaccines also showed considerable efficacy for glioma treatments.

Hyperbaric Oxygen Therapy as an Alternative Therapeutic Option for Radiation-Induced Necrosis Following Radiotherapy for Intracranial Pathologies.

BACKGROUND: Radiotherapy (RT) is a feasible adjuvant therapeutic option for managing intracranial pathologies. One of the late complications of RT that frequently develops within months following RT is radiation necrosis (RN). Corticosteroids are the first-line therapeutic option for RNs; however, in case of unfavorable outcomes or intolerability, several other options, including bevacizumab, laser interstitial thermal therapy, surgery, and hyperbaric oxygen therapy (HBOT). Our goal was to investigate the feasibility and efficacy of the application of HBOT in RNs following RT and help physicians make decisions based on the latest data in the literature. METHODS: We provide a comprehensive review of the literature on the current issues of utilization of HBOT in RNs. RESULTS: We included 11 studies with a total of 46 patients who underwent HBOT. Most of the cases were diagnosed with brain tumors or arteriovenous malformations. Improvement was achieved in most of the cases. DISCUSSION: HBOT is a noninvasive therapeutic intervention that can play a role in adjuvant therapy concurrent with RT and chemotherapy and treating RNs. HBOT resolves the RN through 3 mechanisms, including angiogenesis, anti-inflammatory modulation, and cellular repair. Previous studies demonstrated that HBOT is a feasible and well-tolerated therapeutic option that has shown promising results in improving clinical and radiological outcomes in intracranial RNs. Complications of HBOT are usually mild and reversible. CONCLUSIONS: HBOT is a feasible and effective therapeutic option in steroid-refractory RNs and is associated with favorable outcomes and a low rate of side effects.

Intrathecal injection of human placental mesenchymal stem cells derived exosomes significantly improves functional recovery in spinal cord injured rats.

BACKGROUND: Spinal cord injury (SCI) due to lack of restoration of damaged neuronal cells is associated with sensorimotor impairment. This study was focused on using the human placental mesenchymal stem cells- exosome (HPMSCs- Exosomes) in an animal model of severe SCI under myelogram procedure. METHODS AND RESULTS: Intrathecal injection of exosomes was performed in the acute phase of SCI in female rats. The improved functional recovery of the animals was followed for 6 weeks in control (saline, n = 6) and HPMSCs- EXO (HPMSCs-Exosomes, n = 6) groups. Pathological changes and glial scar size were evaluated. The Immunohistochemistry (IHC) of GFAP and NF200 factors as well as the apoptosis assay was investigated in the tissue samples from the injury site. The results demonstrated that HPMSCs-exosomes can improve motor function by attenuating apoptosis of neurons at the injury site, decreasing GFAP expression and increasing NF200 in the HPMSCs-EXO group. Also, HPMSCs-exosomes by preventing the formation of cavities causes preservation of tissue in SCI rats. CONCLUSIONS: These findings demonstrate the effectiveness of HPMSC-Exosomes as a therapeutic method to improve functional recovery, reduce pathological changes associated with injury, and prevent chronicity after SCI. The neuroprotective and anti-apoptotic potential of HPMSCs- Exosomes may be a promising therapeutic approach for SCI. Another result was the importance of intrathecal injection of exosomes in the acute phase, which accelerated the healing process. Furthermore, the myelogram can be a feasible and suitable method to confirm the accuracy of intrathecal injection and examine the subarachnoid space in the laboratory animals.

Effects of Preoperative Use of Povidone-Iodine-Impregnated Dressing on Postoperative Rate of Surgical Site Infection in Patients Undergoing Posterolateral Lumbar Spinal Fusion Surgery: A Randomized, Nonblinded, Active-Controlled Trial.

BACKGROUND AND OBJECTIVES: No study has evaluated the efficacy of using preoperative antiseptic dressings in reducing the rate of surgical site infection (SSI) in spine surgery thus far. To investigate the efficacy of the use of preoperative povidone-iodine-impregnated antiseptic dressings in patients undergoing instrumented posterolateral lumbar spinal fusion. METHODS: This was a randomized, nonblinded, active-controlled, parallel-group clinical trial. Patients were randomly assigned to the 2 study groups, including treatment and control. Patients in the treatment group received povidone-iodine-impregnated antiseptic dressing applied to the anticipated incision site 12 hours before the operation. The control group merely received the standard perioperative care with no additional intervention or placebo. Patients were followed up for 90 days, and SSIs were recorded. RESULTS: A total of 200 patients were included in this study (100 in each arm). Three cases of SSI were observed in the treatment group compared with 12 in the control one. A significant reduction in the postoperative rate of SSI was observed in the treatment group compared with the control one (P = .029). In addition to study intervention (P = .029), body mass index (P = .005), smoking status (P = .005), duration of the procedure (P = .003), American Society of Anesthesiologists class (P = .002), and diabetes mellitus (P < .001) were significantly associated with the postoperative rate of SSI. CONCLUSION: To the best of our knowledge, this study for the first time showed that preoperative use of antiseptic dressings is significantly effective in reducing the rate of SSI in instrumented posterior lumbar spinal fusion surgery. Future studies are warranted to evaluate the efficacy of different preparations or the effectiveness of the present one in patients undergoing spine procedures with other surgical characteristics.

Beneficial effects of the combination of BCc1 and Hep-S nanochelating-based medicines on IL-6 in hospitalized moderate COVID-19 adult patients: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: In the severe forms of COVID-19 and many other infectious diseases, the patients develop a cytokine storm syndrome (CSS) where pro-inflammatory cytokines such as IL-6 and TNF-α play a key role in the development of this serious process. Selenium and iron are two important trace minerals, and their metabolism is tightly connected to immune system function. Numerous studies highlight the role of selenium and iron metabolism changes in the procedure of COVID-19 inflammation. The immunomodulator effect of nanomedicines that are synthesized based on nanochelating technology has been proved in previous studies. In the present study, the effects of the combination of BCc1(with iron-chelating property) and Hep-S (containing selenium) nanomedicines on mentioned cytokines levels in hospitalized moderate COVID-19 patients were evaluated. METHODS: Laboratory-confirmed moderate COVID-19 patients were enrolled to participate in a randomized, double-blind, placebo-controlled study in two separate groups: combination of BCc1 and Hep-S (N = 62) (treatment) or placebo (N = 60) (placebo). The blood samples were taken before medications on day zero, at discharge, and 28 days after consumption to measure hematological and biochemical parameters and cytokine levels. The clinical symptoms of all the patients were recorded according to an assessment questionnaire before the start of the treatment and on days 3 and discharge day. RESULTS: The results revealed that consumption of the nanomedicines led to a significant decrease in the mean level of IL-6 cytokine, and at the end of the study, there was a 77% downward trend in IL-6 in the nanomedicine group, while an 18% increase in the placebo group (p < 0.05). In addition, the patients in the nanomedicines group had lower TNF-α levels; accordingly, there was a 21% decrease in TNF-α level in the treatment group, while a 31% increase in this cytokine level in the placebo was observed (p > 0.05). On the other hand, in nanomedicines treated groups, clinical scores of coughing, fatigue, and need for oxygen therapy improved. CONCLUSIONS: In conclusion, the combination of BCc1 and Hep-S inhibits IL-6 as a highly important and well-known cytokine in COVID-19 pathophysiology and presents a promising view for immunomodulation that can manage CSS. TRIAL REGISTRATION: Iranian Registry of Clinical Trials RCT20170731035423N2 . Registered on June 12, 2020.

Management of Glioblastoma Multiforme During the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic: A Review of the Literature.

BACKGROUND: Patients with glioblastoma multiforme (GBM) and other patients with cancer are at a greater risk of developing severe complications as a result of coronavirus disease 2019 (COVID-19) infection. Therefore, it is crucial to adjust therapeutic approaches to reduce exposure and complications and achieve the most appropriate treatment outcomes. OBJECTIVE: Our goal was to help physicians to make decisions based on the latest data in the literature. METHOD: We provide a comprehensive review of the literature on the current issues of GBM and COVID-19 infection. RESULTS: The mortality of patients with diffuse glioma as a result of COVID-19 infection was 39%, which is higher than in the general population. The statistics showed that 84.5% of patients with diagnosed brain cancer (mostly GBM) and 89.9% of their caregivers received COVID-19 vaccines. The decision to apply different therapeutic approaches must be made individually based on age, tumor grade, molecular profile, and performance status. The advantages and disadvantages of adjuvant radiotherapy and chemotherapy after the surgery should be evaluated carefully. In the setting of the follow-up period, special considerations must be considered to minimize COVID-19 exposure. CONCLUSIONS: The pandemic altered medical approaches worldwide, and the management of patients in an immunocompromised state, such as patients with GBM, is challenging; therefore, special considerations must be considered.

Gliomatosis cerebri with blindness: A case report with literature review.

Cerebral gliomatosis (GC) is a rare diffuse infiltrative growth pattern of glioma with nonspecific clinical manifestations like visual impairment that may involve bilateral temporal lobes. Herpes simplex encephalitis (HSE) and limbic encephalitis (LE) can also lead to temporal lobe involvement. Differentiating these entities is necessary for patients with misleading presentations and imaging findings. To the best of our knowledge, this is the third case of GC presenting with blindness. The patient was a 35 years-old male in a drug rehabilitation center for heroin addiction. He presented with a headache, a single episode of seizure, and a 2-month history of bilateral decrease in visual acuity, which had acutely worsened. Magnetic resonance imaging (MRI) and computed tomography (CT) showed bilateral temporal lobe involvement. Ophthalmological studies showed bilateral papilledema, absence of visual evoked potential, and thickening of the retinal nerve fiber layer. Due to this clinical presentation, normal laboratory data, and suspicious MRI findings, further investigation with magnetic resonance spectroscopy (MRS) was performed. Results showed a greatly increased ratio of choline to creatinine(Cr) or N-acetyl aspartate (NAA), suggesting a neoplastic nature of the disease. Subsequently, the patient was referred for a brain tissue biopsy with a suspicion of malignancy. The pathology results revealed adult-type diffuse glioma with isocitrate dehydrogenase (IDH) mutation. Bilateral blindness, as well as bilateral temporal lobe involvement, each has many different causes. However, as demonstrated in this study, adult-type diffuse glioma must be considered a rare cause of concomitant bilateral temporal lobe involvement and blindness.

The Influence of the Substrate on the Functionality of Spin Crossover Molecular Materials.

Spin crossover complexes are a route toward designing molecular devices with a facile readout due to the change in conductance that accompanies the change in spin state. Because substrate effects are important for any molecular device, there are increased efforts to characterize the influence of the substrate on the spin state transition. Several classes of spin crossover molecules deposited on different types of surface, including metallic and non-metallic substrates, are comprehensively reviewed here. While some non-metallic substrates like graphite seem to be promising from experimental measurements, theoretical and experimental studies indicate that 2D semiconductor surfaces will have minimum interaction with spin crossover molecules. Most metallic substrates, such as Au and Cu, tend to suppress changes in spin state and affect the spin state switching process due to the interaction at the molecule-substrate interface that lock spin crossover molecules in a particular spin state or mixed spin state. Of course, the influence of the substrate on a spin crossover thin film depends on the molecular film thickness and perhaps the method used to deposit the molecular film.

Suicide gene therapy using allogeneic adipose tissue-derived mesenchymal stem cell gene delivery vehicles in recurrent glioblastoma multiforme: a first-in-human, dose-escalation, phase I clinical trial.

BACKGROUND: Glioblastoma multiforme (GBM) is associated with remarkably poor prognosis, and its treatment is challenging. This investigation aimed to evaluate the safety of suicide gene therapy using allogeneic adipose tissue-derived mesenchymal stem cells (ADSCs) carrying herpes simplex virus-thymidine kinase (HSV-TK) gene for the first time in patients with recurrent GBM. METHODS: This study was a first-in-human, open-label, single-arm, phase I clinical trial with a classic 3 + 3 dose escalation design. Patients who did not undergo surgery for their recurrence were included and received this gene therapy protocol. Patients received the intratumoral stereotactic injection of ADSCs according to the assigned dose followed by prodrug administration for 14 days. The first dosing cohort (n = 3) received 2.5 × 105 ADSCs; the second dosing cohort (n = 3) received 5 × 105 ADSCs; the third dosing cohort (n = 6) received 10 × 105 ADSCs. The primary outcome measure was the safety profile of the intervention. RESULTS: A total of 12 patients with recurrent GBM were recruited. The median follow-up was 16 (IQR, 14-18.5) months. This gene therapy protocol was safe and well tolerated. During the study period, eleven (91.7%) patients showed tumor progression, and nine (75.0%) died. The median overall survival (OS) was 16.0 months (95% CI 14.3-17.7) and the median progression-free survival (PFS) was 11.0 months (95% CI 8.3-13.7). A total of 8 and 4 patients showed partial response and stable disease, respectively. Moreover, significant changes were observed in volumetric analysis, peripheral blood cell counts, and cytokine profile. CONCLUSIONS: The present clinical trial, for the first time, showed that suicide gene therapy using allogeneic ADSCs carrying the HSV-TK gene is safe in patients with recurrent GBM. Future phase II/III clinical trials with multiple arms are warranted to validate our findings and further investigate the efficacy of this protocol compared with standard therapy alone. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT), IRCT20200502047277N2. Registered 8 October 2020, https://www.irct.ir/ .

Optical characterization of isothermal spin state switching in an Fe(II) spin crossover molecular and polymer ferroelectric bilayer.

Using optical characterization, it is evident that the spin state of the spin crossover molecular complex [Fe{H2B(pz)2}2(bipy)] (pz = tris(pyrazol-1-1y)-borohydride, bipy = 2,2'-bipyridine) depends on the electric polarization of the adjacent polymer ferroelectric polyvinylidene fluoride-hexafluoropropylene (PVDF-HFP) thin film. The role of the PVDF-HFP thin film is significant but complex. The UV-Vis spectroscopy measurements reveals that room temperature switching of the electronic structure of [Fe{H2B(pz)2}2(bipy)] molecules in bilayers of PVDF-HFP/[Fe{H2B(pz)2}2(bipy)] occurs as a function of ferroelectric polarization. The retention of voltage-controlled nonvolatile changes to the electronic structure in bilayers of PVDF-HFP/[Fe{H2B(pz)2}2(bipy)] strongly depends on the thickness of the PVDF-HFP layer. The PVDF-HFP/[Fe{H2B(pz)2}2(bipy)] interface may affect PVDF-HFP ferroelectric polarization retention in the thin film limit.

Case report: Stem cell-based suicide gene therapy mediated by the herpes simplex virus thymidine kinase gene reduces tumor progression in multifocal glioblastoma.

Introduction: The prognosis for glioblastoma multiforme (GBM), a malignant brain tumor, is poor despite recent advancements in treatments. Suicide gene therapy is a therapeutic strategy for cancer that requires a gene to encode a prodrug-activating enzyme which is then transduced into a vector, such as mesenchymal stem cells (MSCs). The vector is then injected into the tumor tissue and exerts its antitumor effects. Case presentation: A 37-year-old man presented to our department with two evident foci of glioblastoma multiforme at the left frontal and left parietal lobes. The patient received an injection of bone marrow-derived MSCs delivering the herpes simplex virus thymidine kinase (HSV-tk) gene to the frontal focus of the tumor, followed by ganciclovir administration as a prodrug for 14 days. For follow-up, the patient was periodically assessed using magnetic resonance imaging (MRI). The growth and recurrence patterns of the foci were assessed. After the injection on 09 February 2019, the patient's follow-up appointment on 19 December 2019 MRI revealed a recurrence of parietal focus. However, the frontal focus had a slight and unremarkable enhancement. On the last follow-up (18 March 2020), the left frontal focus had no prominent recurrence; however, the size of the left parietal focus increased and extended to the contralateral hemisphere through the corpus callosum. Eventually, the patient passed away on 16 July 2020 (progression-free survival (PFS) = 293 days, overall survival (OS) = 513 days). Conclusion: The gliomatous focus (frontal) treated with bone marrow-derived MSCs carrying the HSV-TK gene had a different pattern of growth and recurrence compared with the non-treated one (parietal). Trial registration: IRCT20200502047277N2. Registered 10 May 2020-Retrospectively registered, https://eng.irct.ir/trial/48110.

Electronic structure of cobalt valence tautomeric molecules in different environments.

Future molecular microelectronics require the electronic conductivity of the device to be tunable without impairing the voltage control of the molecular electronic properties. This work reports the influence of an interface between a semiconducting polyaniline polymer or a polar poly-D-lysine molecular film and one of two valence tautomeric complexes, i.e., [CoIII(SQ)(Cat)(4-CN-py)2] ↔ [CoII(SQ)2(4-CN-py)2] and [CoIII(SQ)(Cat)(3-tpp)2] ↔ [CoII(SQ)2(3-tpp)2]. The electronic transitions and orbitals are identified using X-ray photoemission, X-ray absorption, inverse photoemission, and optical absorption spectroscopy measurements that are guided by density functional theory. Except for slightly modified binding energies and shifted orbital levels, the choice of the underlying substrate layer has little effect on the electronic structure. A prominent unoccupied ligand-to-metal charge transfer state exists in [CoIII(SQ)(Cat)(3-tpp)2] ↔ [CoII(SQ)2(3-tpp)2] that is virtually insensitive to the interface between the polymer and tautomeric complexes in the CoII high-spin state.

Safety and Potential Efficacy of Selective Dorsal Rhizotomy in Adults with Spinal Cord Injury-Induced Spasticity: An Open-Label, Non-Randomized, Single-Arm Trial.

BACKGROUND: Despite the abundant literature on the use of selective dorsal rhizotomy (SDR) in spastic cerebral palsy, no investigation has evaluated its use in adult patients with chronic spinal cord injury (SCI)-induced spasticity. The present investigation aimed to evaluate the safety and potential efficacy of SDR in chronic SCI-induced spasticity for the first time. METHODS: In this open-label, single-arm, non-randomized clinical trial, all patients were assigned to the single study intervention arm and underwent SDR. The primary outcome measure was the safety profile of SDR. Secondary outcome measures were Modified Ashworth Scale, Penn Spasm Frequency Scale, visual analog scale for spasticity, Spinal Cord Injury Spasticity Tool, Spinal Cord Independence measure version III, and Short Form 36 Health Survey Questionnaire. RESULTS: Six patients with cervical SCI and 4 with thoracic SCI were allocated to the single study intervention arm. No adverse event attributable to the SDR was found. Moreover, all secondary outcome measures of the study improved significantly over the study period (P < 0.001). Multiple regression analysis also found a significant association between level of injury and changes in average Modified Ashworth Scale scores (P = 0.041), Spinal Cord Injury Spasticity Tool score (P = 0.013), and Spinal Cord Independence measure version III total (P = 0.002) and mobility domain scores (P = 0.004) at 12-month postoperatively. CONCLUSIONS: This clinical trial indicated that SDR is a safe and potentially effective procedure in patients with severe and intractable SCI-induced spasticity. However, future clinical trials with larger sample sizes and adequate power are required to validate our findings regarding efficacy.

Global and Regional DNA methylation silencing of PPARγ Associated with Glioblastoma Multiforme Pathogenesis.

BACKGROUND: The relationship between peroxisome proliferator-activated receptor gamma (PPARγ) expression level and epigenetic modifications occurring in glioblastoma multiforme (GBM) pathogenesis is largely unknown. Herein, we examine the association of PPARγ expression with its promoter and genomic global DNA methylation status, as well as DNA methyltransferases (DNMTs) gene expression in GBM patients. METHODS: We examined the patterns of promoter methylation and PPARγ expression in 26 GBM tissues and 13 adjacent non-tumor tissues by methylation-specific PCR (MSP), real-time PCR, and ELISA, respectively. Also, we examined the genomic global 5-methyl cytosine levels and DNMTs gene expression using ELISA and real-time PCR methods, respectively. RESULTS: We found that hypermethylation on a specific region of the PPARγ promoter is significantly associated with the downregulation of the PPARγ gene and protein level in GBM patients. Interestingly, the amount of 5-methyl cytosine level was significantly reduced in GBM patients and positively correlated with PPARγ protein expression. Furthermore, the expression level of DNMT1, DNMT3A, and 3B were upregulated in GBM patients and the average expression level of all three DNMTs was positively correlated with tumor area. Also, we found that tumors from cortical regions exhibited a higher global DNA hypomethylation and PPARγ hypermethylation was related to the increase in GBM risk. CONCLUSION: Our study demonstrated that global DNA methylation and PPARγ epigenetic silencing is associated with the GBM risk. Our data provide a novel molecular mechanistic insight into epigenetic silencing of PPARγ in GBM patients that may be relevant as a key tumor marker for GBM pathogenesis.

Promising effects of corticosteroid treatment in combination with antifungal agents in a patient with Aspergillus meningitis.

Although Aspergillus meningitis is poorly responsive to current guidelines for treatment, we describe a dramatic response of Aspergillus meningitis in a patient to treatment using a combination of corticosteroids with guideline's suggested antifungal agents. Administration of corticosteroids in patients with Aspergillus meningitis is rarely reported in previous studies.