The risk of dementia with increased body mass index

BACKGROUND: identification of modifiable risk factors is crucial in the prevention of dementia, given its limited treatment options. Studies on increased body mass index (BMI) as a risk factor for dementia show conflicting results. METHODS: we systematically retrieved and reviewed longitudinal population-based studies on increased BMI and dementia using a standard protocol. We searched Medline (1966-2006), Ageline (1978-2006), PsychInfo (1966-2006), CINAHL (1982-2006), and other relevant databases, including the reference lists of the eligible articles for review. Included studies were subjected to a quality assessment protocol. RESULTS: we identified eight studies that met our selection criteria. These studies covered 1,688 cases of dementia from 28,697 participants. After adjustment for age, smoking, comorbidities, and other confounders, four studies presented significantly increased risk of dementia with elevated BMI. CONCLUSION: this systematic review supports the hypothesis that increased BMI is independently associated with increased risk of dementia. Long-term studies to examine the mechanisms underlying the relationship between obesity and dementia are needed.     

Hypermethylation of MCAM gene is associated with advanced tumor stage in prostate cancer

BACKGROUND: DNA methylation has emerged as a promising biomarker for prostate cancer detection. In this report, we screened 36 candidate genes generated by a bioinformatic analysis of the human genome, and found that the melanoma cell adhesion molecule (MCAM) was an excellent candidate for cancer-specific methylation in prostate cancer. METHODS: Direct sequencing of bisulfite-treated genomic DNA, conventional methylation-specific PCR (MSP), real-time quantitative methylation-specific PCR, immunohistochemistry, colony formation assay, and statistical analysis. RESULTS: We found that the melanoma cell adhesion molecule (MCAM) gene promoter was specifically methylated in prostate cancer cell lines and primary prostate cancer (PCa) but not in non-neoplastic prostate (BPH) tissues by direct sequencing of bisulfite-treated genomic DNA and conventional methylation-specific PCR (MSP). Further analysis with quantitative MSP showed greater hypermethylation of the MCAM promoter (80%, 70/88) in primary prostate cancer compared to 12.5% (3/24) in BPH. Prostatic intraepithelial neoplasias (PIN), potential precursors of prostate carcinoma, showed an intermediate methylation rate of 23% (7/30). We further observed that MCAM promoter methylation was directly correlated with tumor stage (pT3+pT4) (P = 0.001) and Gleason score (P = 0.018) in primary prostate carcinoma. CONCLUSIONS: Our results suggest that MCAM promoter hypermethylation deserves further attention as a potential diagnostic prostatic DNA marker in human prostate cancer.     

Histological Aggressiveness of Fluorodeoxyglucose Positron-Emission Tomogram (FDG-PET)-Detected Incidental Thyroid Carcinomas

Background We previously reported a high incidence of primary thyroid cancer in fluorodeoxyglucose positron-emission tomogram (FDG-PET)-detected incidental thyroid abnormalities. The aim of our study was to determine if these FDG-PET-detected thyroid malignancies represent a more-aggressive variant of primary thyroid carcinoma. Materials and methods All patients that underwent operative intervention for FDG-PET-detected incidental thyroid abnormalities were identified (June 2003 to April 2006). Patients with a diagnosis of primary thyroid carcinoma on final histopathology were included in the study. The patient demographics and histopathological findings were analyzed to identify adverse prognostic features. Results In 11,500 patients, 17,250 FDG-PET scans were performed; 377 of these patients (3.2% of patients and 2.1% of FDG-PET scans) had findings positive for thyroid abnormality. Of the 32 patients that underwent operative intervention, 22 patients with a final diagnosis of primary thyroid malignancy were included in the study. A greater number of patients [12 patients, (54%)] were noted to harbor poor prognostic variants of primary thyroid carcinoma on final histopathology [tall-cell variant: 11 patients (50%) and poorly differentiated thyroid carcinoma: 1 patient (4%)]. Extra-thyroidal extension (ETE) was noted in the majority of patients [14 patients (63%)]. In patients with tall cell variant on final histopathology, the rate of ETE was even higher [10 patients (90%)]. Conclusion Thyroid malignancies incidentally detected on FDG-PET scan harbor a high rate of unfavorable prognostic features and may represent a more-aggressive variant of primary thyroid carcinoma. These patients need to be subjected to further investigation with a view to possible operative intervention.     

LOXL1 and LOXL4 are epigenetically silenced and can inhibit ras/extracellular signal-regulated kinase signaling pathway in human bladder cancer

Promoter hypermethylation is one of the common mechanisms leading to gene silencing in various human cancers. Using a combination of pharmacologic unmasking and microarray techniques, we identified 59 candidate hypermethylated genes, including LOXL1, a lysyl oxidase-like gene, in human bladder cancer cells. We further showed that LOXL1 and LOXL4 are commonly silenced genes in human bladder cancer cells, and this silence is predominantly related to promoter methylation. We also found LOXL1 and LOXL4 gene methylation and loss of expression in primary bladder tumors. In addition, somatic mutations were identified in LOXL4, but not in LOXL1 in bladder cancer. Moreover, reintroduction of LOXL1 and LOXL4 genes into human bladder cancer cells leads to a decrease of colony formation ability. Further studies indicated that the overexpression of LOXL1 and LOXL4 could antagonize Ras in activating the extracellular signal-regulated kinase (ERK) signaling pathway. Thus, our current study suggests for the first time that lysyl oxidase-like genes can act as tumor suppressor genes and exert their functions through the inhibition of the Ras/ERK signaling pathway in human bladder cancer.     

Quantitative hypermethylation of NMDAR2B in human gastric cancer

NMDA receptor Type 2B (NMDAR2B) is a candidate TSG first identified in esophageal squamous cell carcinoma (ESCC). To evaluate NMDAR2B methylation in gastric cancer progression, we performed quantitative methylation-specific PCR (MSP), RT-PCR and immnunohistochemistry (IHC) in primary gastric tissues and colony formation assays in gastric cancer cell lines. We found that the expression of NMDAR2B was reactivated by the demethylating agent, 5-aza-2'-deoxycytidine, with or without trichostatin A in gastric cancer cell lines. Moreover, inactivation of NMDAR2B was found to be closely correlated with promoter methylation status in gastric cell lines and primary gastric tumors. IHC data also showed that NMDAR2B was specifically expressed in gastric epithelial cells and its expression was diminished or absent in gastric cancer epithelium. Quantitative analysis of NMDAR2B promoter methylation showed 61% (17/28) hypermethylation in primary gastric tumors versus 5% (1/20) in normal gastric tissues from nongastric cancer patients. Forced over-expression of NMDAR2B in gastric cancer cell lines significantly inhibited cell colony formation. Taken together, the above results suggest that NMDAR2B methylation is a common and important biologically relevant event in gastric cancer progression.     

A Role for Extracellular Vesicles in SARS-CoV-2 Therapeutics and Prevention

Extracellular vesicles (EVs) are the common designation for ectosomes, microparticles and microvesicles serving dominant roles in intercellular communication. Both viable and dying cells release EVs to the extracellular environment for transfer of cell, immune and infectious materials. Defined morphologically as lipid bi-layered structures EVs show molecular, biochemical, distribution, and entry mechanisms similar to viruses within cells and tissues. In recent years their functional capacities have been harnessed to deliver biomolecules and drugs and immunological agents to specific cells and organs of interest or disease. Interest in EVs as putative vaccines or drug delivery vehicles are substantial. The vesicles have properties of receptors nanoassembly on their surface. EVs can interact with specific immunocytes that include antigen presenting cells (dendritic cells and other mononuclear phagocytes) to elicit immune responses or affect tissue and cellular homeostasis or disease. Due to potential advantages like biocompatibility, biodegradation and efficient immune activation, EVs have gained attraction for the development of treatment or a vaccine system against the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection. In this review efforts to use EVs to contain SARS CoV-2 and affect the current viral pandemic are discussed. An emphasis is made on mesenchymal stem cell derived EVs’ as a vaccine candidate delivery system.

Graphical Abstract

     

Radio frequency coil technology for small-animal MRI

A review of the theory, technology, and use of radio frequency (RF) coils for small-animal MRI is presented. It includes a brief overview of MR signal-to-noise (S/N) analysis and discussions of the various coils commonly used in small-animal MR: surface coils, linear volume coils, birdcages, and their derivatives. The scope is limited to mid-range coils, i.e. coils where the product (fd) of the frequency f and the coil diameter d is in the range 2-30 MHz-m. Common applications include mouse brain and body coils from 125 to 750 MHz, rat body coils up to 500 MHz, and small surface coils at all fields. In this regime, all the sources of loss (coil, capacitor, sample, shield, and transmission lines) are important. All such losses may be accurately captured in some modern full-wave 3D electromagnetics software, and new simulation results are presented for a selection of surface coils using Microwave Studio 2006 by Computer Simulation Technology, showing the dramatic importance of the "lift-off effect". Standard linear circuit simulators have been shown to be useful in optimization of complex coil tuning and matching circuits. There appears to be considerable potential for trading S/N for speed using phased arrays, especially for a larger field of view. Circuit simulators are shown to be useful for optimal mismatching of ultra-low-noise preamps based on the enhancement-mode pseudomorphic high-electron-mobility transistor for optimal coil decoupling in phased arrays. Cryogenically cooled RF coils are shown to offer considerable opportunity for future gains in S/N in smaller samples.