Downregulation of miR-29a as a possible diagnostic biomarker for schizophrenia.

BACKGROUND: MicroRNAs (miRNAs) are epigenetic factors regulating many genes involved in brain development. Dysregulation of miRNA could result in dysregulation of genes which may contribute to diseases affecting the brain and behavior (e.g., schizophrenia). miR-29 family is a miRNA family contributing to brain maturation. miR-29 knockout in animal studies is reported to correlate with psychiatric disorders very similar to those seen in schizophrenia. In this study, we aimed to evaluate the miR-29a level in patients with schizophrenia and its potential value in the diagnosis of schizophrenia. MATERIALS AND METHODS: The serum sample of 42 patients with schizophrenia and 40 healthy subjects were obtained from the Azeri Recent onset/Acute phase psychosis Survey (ARAS) Cohort study. After preparations, the expression level of miR-29a was investigated by real-time PCR. The SPSS and GraphPad prism software were used to analyze the relation between miR-29a level and clinical parameters and its potential as a biomarker for the diagnosis of schizophrenia. RESULTS: Our study showed a significantly lower miR-29a level in patients compared to healthy controls (p = 0.0012). Furthermore, miR-29a level was significantly lower in some types of schizophrenia (p = 0.024). miR-29a level was not related to sex, age, or heredity (p > 0.05). miR-29a also showed 80% specificity and 71.43% sensitivity in the diagnosis of schizophrenia. CONCLUSION: Downregulation of miR-29a in schizophrenia is significantly related to the development of this illness. It might have the potential as a biomarker for schizophrenia.

Towards A Wireless Image Sensor for Real-Time Fluorescence Microscopy in Cancer Therapy.

We present a mm-sized, ultrasonically powered lensless CMOS image sensor as a progress towards wireless fluorescence microscopy. Access to biological information within the tissue has the potential to provide insights guiding diagnosis and treatment across numerous medical conditions including cancer therapy. This information, in conjunction with current clinical imaging techniques that have limitations in obtaining images continuously and lack wireless compatibility, can improve continual detection of multicell clusters deep within tissue. The proposed platform incorporates a 2.4×4.7 mm2 integrated circuit (IC) fabricated in TSMC 0.18 µm, a micro laser diode (µLD), a single piezoceramic and off-chip storage capacitors. The IC consists of a 36×40 array of capacitive trans-impedance amplifier-based pixels, wireless power management and communication via ultrasound and a laser driver all controlled by a Finite State Machine. The piezoceramic harvests energy from the acoustic waves at a depth of 2 cm to power up the IC and transfer 11.5 kbits/frame via backscattering. During Charge-Up, the off-chip capacitor stores charge to later supply a high-power 78 mW µLD during Imaging. Proof of concept of the imaging front end is shown by imaging distributions of CD8 T-cells, an indicator of the immune response to cancer, ex vivo, in the lymph nodes of a functional immune system (BL6 mice) against colorectal cancer consistent with the results of a fluorescence microscope. The overall system performance is verified by detecting 140 µm features on a USAF resolution target with 32 ms exposure time and 389 ms ultrasound backscattering.

Towards A Wireless Image Sensor for Real-Time Fluorescence Microscopy in Cancer Therapy.

We present a mm-sized, ultrasonically powered lensless CMOS image sensor as a progress towards wireless fluorescence microscopy. Access to biological information within the tissue has the potential to provide insights guiding diagnosis and treatment across numerous medical conditions including cancer therapy. This information, in conjunction with current clinical imaging techniques that have limitations in obtaining images continuously and lack wireless compatibility, can improve continual detection of multicell clusters deep within tissue. The proposed platform incorporates a 2.4×4.7 mm2 integrated circuit (IC) fabricated in TSMC 0.18 µm, a micro laser diode (µLD), a single piezoceramic and off-chip storage capacitors. The IC consists of a 36×40 array of capacitive trans-impedance amplifier-based pixels, wireless power management and communication via ultrasound and a laser driver all controlled by a Finite State Machine. The piezoceramic harvests energy from the acoustic waves at a depth of 2 cm to power up the IC and transfer 11.5 kbits/frame via backscattering. During Charge-Up, the off-chip capacitor stores charge to later supply a high-power 78 mW µLD during Imaging. Proof of concept of the imaging front end is shown by imaging distributions of CD8 T-cells, an indicator of the immune response to cancer, ex vivo, in the lymph nodes of a functional immune system (BL6 mice) against colorectal cancer consistent with the results of a fluorescence microscope. The overall system performance is verified by detecting 140 µm features on a USAF resolution target with 32 ms exposure time and 389 ms ultrasound backscattering.

A Highly Robust Medical Image Watermarking Method for Medical Real-time Applications.

Background: Watermarking such as other security concepts is an ongoing challenging research issue, especially for medical images, to protect patient privacy. Medical images need to be shared and transferred between hospitals and specialists as quickly as possible for better diagnosis. Fast and simple watermarking is needed as well as the robust transferring of channel noise, such as salt and pepper noise and robust cropping that may occur from specialists and signature encryption for patient privacy. Methods: In this article, a highly robust and simple watermarking method is introduced. The proposed method has very low computational complexity and at the same time, it is very robust to interference and uses simple computations such as (XORs) Exclusive ORs and rotations that can be done in real-time. The proposed method uses a combination of hidden neighboring signature information, Sudoku permutation, and noise pre-processing to achieve high robustness against salt and pepper noise and cropping. Simple signature encryption is also used. Results: The proposed method is examined in different medical image datasets. The experimental results indicate the proposed watermarking system is robust to salt and pepper noise density of up to 90% and about 70% cropping. The number of computations including encryption is five XOR per pixel and a rotation per block of signature size. Conclusion: A novel method for medical image watermarking is presented. The proposed method is in the spatial domain, has encryption, and uses only XOR computation. The proposed method is highly robust to noise and cropping which is necessary for medical uses. The proposed method can be used efficiently for real-time watermarking for medical and nonmedical image datasets.

An updated review on the significance of DNA and protein methyltransferases and de-methylases in human diseases: From molecular mechanism to novel therapeutic approaches.

Epigenetic mechanisms are crucial in regulating gene expression. These mechanisms include DNA methylation and histone modifications, like methylation, acetylation, and phosphorylation. DNA methylation is associated with gene expression suppression; however, histone methylation can stimulate or repress gene expression depending on the methylation pattern of lysine or arginine residues on histones. These modifications are key factors in mediating the environmental effect on gene expression regulation. Therefore, their aberrant activity is associated with the development of various diseases. The current study aimed to review the significance of DNA and histone methyltransferases and demethylases in developing various conditions, like cardiovascular diseases, myopathies, diabetes, obesity, osteoporosis, cancer, aging, and central nervous system conditions. A better understanding of the epigenetic roles in developing diseases can pave the way for developing novel therapeutic approaches for affected patients.

Genetic Diversity Assessment of Iranian Kentucky Bluegrass Accessions: II. Nuclear DNA Content and Its Association with Morphological and Geographical Features.

Poa pratensis L. is a perennial turfgrass with high regeneration and fertility, resistance to cold and drought, and quick colonization. By facultative apomixis, this plant can create a wide range of ploidy levels (2n = 22 to 2n = 154), resulting in a wide range of chromosomal numbers and sexual and apomictic reproductive diversity. The plant materials included fifty accessions from Iran's Center, South, North, North-East, North-West, and West ecoregions. UPOV standards were used to measure the qualities that were researched. The squash technique of chromosome counting revealed that Iranian Kentucky bluegrass accessions had chromosomal counts ranging from 24 to 87. The relative sizes of the 2C genomes were measured using laser flow cytometry. The range of DNA content was fairly wide, ranging from 4.92 to 11.52 pg. DNA content has a strong positive correlation with elevation, a moderately positive correlation with flag leaf length and leaf sheath width, and a negative correlation with inflorescence anthocyanin color and leaf anthocyanin color. The genotypes and ecological zones of this plant in Iran were distinguished based on morphological diversity and DNA content. The results from this study could be useful in identifying and studying wild Kentucky bluegrass genotypes. It aids in predicting the location of rare genotypes used as breeding materials. It can also increase the plant's variability for future generations by introducing new ecotypes, with particular genomic and morphological traits, to previously cultivated populations. We expect that the findings of this study will aid in understanding the evolution of this plant in the context of Iran's climatic variety.

Accidental release of chlorine from a cylinder during transport and an emergency response plan: A scenario-based study.

INTRODUCTION: This article summarizes our research study on the scenario of an accidental chlorine gas release during transportation and preparing emergency response plan to mitigate the subsequent hazards in urban areas. METHODOLOGY: To conduct the research study, the event tree analysis (ETA), a series of brain storming sessions, and a modeling of consequences of an accident using the Phylogenetic Analysis with Space/Time models (PHAST) software were employed. RESULTS AND DISCUSSION: Based on the result of the event tree, 32 initial occurring paths and 20 eventual occurring paths are identified as the outcome. The evacuation time is about 41 seconds, which is very short, and the odds of casualties are estimated at 99 percent within a radius of 140-192 m from the release site, 50 percent within a radius of 202-599 m, and 1 percent within a radius of 758 m. CONCLUSION: Along with the use of consequence modeling, the development of the ETA can be effective in emergency preparedness. In the case of a chlorine gas release, it would not be possible to effectively control the source of release. Furthermore, the result indicates that in a major city like Tehran, the application and transport of chlorine gas can be a serious challenge.

Ectopic expression of lncRNA MVIH as a potential diagnostic biomarker in cervical cancer.

AIM: Cervical cancer (CC) is one of the most common cancers in women. Recent advances in screening and vaccination against the papilloma virus (HPV) have increased protection against CC. However, there is no effective diagnostic biomarker and treatment approach during the course of the disease. The current study is thus aimed to evaluate the changes in the expression of lncRNA associated with microvascular invasion in hepatocellular carcinoma (lncRNA MVIH) and its diagnostic value as a biomarker in CC patients. MATERIALS AND METHODS: One-hundred and fifteen (n = 115) pairs of CC primary tumor and marginal non-tumor tissue samples were obtained from Tabriz Valiasr International Hospital (Tabriz, Iran). RNA extraction and cDNA synthesis followed by quantitative reverse transcriptase PCR (qRT-PCR) were considered to investigate alterations in the expression levels of MVIH in patients with CC. The associations between MVIH expression changes and clinicopathological features as well as its potential as a diagnostic biomarker were assessed using SPSS and GraphPad prism software and the receiver operating characteristic (ROC). RESULTS: The expression levels of MVIH were significantly higher in CC tumors as compared to marginal non-tumor samples (p < 0.0001). Overexpression of MVIH was significantly associated with younger age (p = 0.033), lymph node metastasis (p = 0.031), tumor invasion depth (p = 0.035), and squamous cell type of CC (p = 0.019). The ROC analysis for MVIH as a diagnostic biomarker revealed the respective sensitivity and specificity of 67.83 and 80. CONCLUSIONS: Overexpression of MVIH in CC tumors suggests its oncogenic role during tumorigenesis. Thus, it may serve as a potential diagnostic biomarker.

Advanced Scalability for Light Field Image Coding.

Light field imaging, which captures both spatial and angular information, improves user immersion by enabling post-capture actions, such as refocusing and changing view perspective. However, light fields represent very large volumes of data with a lot of redundancy that coding methods try to remove. State-of-the-art coding methods indeed usually focus on improving compression efficiency and overlook other important features in light field compression such as scalability. In this paper, we propose a novel light field image compression method that enables (i) viewport scalability, (ii) quality scalability, (iii) spatial scalability, (iv) random access, and (v) uniform quality distribution among viewports, while keeping compression efficiency high. To this end, light fields in each spatial resolution are divided into sequential viewport layers, and viewports in each layer are encoded using the previously encoded viewports. In each viewport layer, the available viewports are used to synthesize intermediate viewports using a video interpolation deep learning network. The synthesized views are used as virtual reference images to enhance the quality of intermediate views. An image super-resolution method is applied to improve the quality of the lower spatial resolution layer. The super-resolved images are also used as virtual reference images to improve the quality of the higher spatial resolution layer. The proposed structure also improves the flexibility of light field streaming, provides random access to the viewports, and increases error resiliency. The experimental results demonstrate that the proposed method achieves a high compression efficiency and it can adapt to the display type, transmission channel, network condition, processing power, and user needs.

Stb6 mediates stomatal immunity, photosynthetic functionality, and the antioxidant system during the Zymoseptoria tritici-wheat interaction.

This study offers new perspectives on the biochemical and physiological changes that occur in wheat following a gene-for-gene interaction with the fungal pathogen Zymoseptoria tritici. The Z. tritici isolate IPO323, carries AvrStb6, while ΔAvrStb6#33, lacks AvrStb6. The wheat cultivar (cv.) Shafir, bears the corresponding resistance gene Stb6. Inoculation of cv. Shafir with these isolates results in two contrasted phenotypes, offering a unique opportunity to study the immune response caused by the recognition of AvrStb6 by Stb6. We employed a variety of methodologies to dissect the physiological and biochemical events altered in cv. Shafir, as a result of the AvrStb6-Stb6 interaction. Comparative analysis of stomatal conductance demonstrated that AvrStb6-Stb6 mediates transient stomatal closures to restrict the penetration of Zymoseptoria tritici. Tracking photosynthetic functionality through chlorophyll fluorescence imaging analysis demonstrated that AvrStb6-Stb6 retains the functionality of photosynthesis apparatus by promoting Non-Photochemical Quenching (NPQ). Furthermore, the PlantCV image analysis tool was used to compare the H2O2 accumulation and incidence of cell death (2, 4, 8, 12, 16, and 21 dpi), over Z. tritici infection. Finally, our research shows that the AvrStb6-Stb6 interaction coordinates the expression and activity of antioxidant enzymes, both enzymatic and non-enzymatic, to counteract oxidative stress. In conclusion, the Stb6-AvrStb6 interaction in the Z. tritici-wheat pathosystem triggers transient stomatal closure and maintains photosynthesis while regulating oxidative stress.

Down-Regulation of CXCR4 in Mesenchymal Stem Cells by Septic Serum.

Background: Sepsis is one of the main concerns of health and one of the leading causes of death in hospitals. It is essential to manage sepsis in hospitalized patients. In recent years, cell therapy has been considered as a new approach to treat sepsis. This study evaluated the effect of CXCR4 as one of the main proteins involved in the homing of mesenchymal stem cells in the sepsis serum in mice model. Methods: Mouse sepsis model was induced by injection of E.coli and biochemical analyses was done to confirm the organ failure. Mesenchymal stem cells (MSCs) derived from bone marrow were separated into sepsis and control groups. In the sepsis serum group, MSCs were treated with sepsis serum at two time points: 24 and 48 h. Quantitative RT-PCR and flow cytometry were performed to determine the mRNA expression of CXCR4 in sepsis serum group compared to control group. Also, a migration assay was done to assess the migration capacity of bone marrow MSCs during inflammation and treatment in sepsis. Results: Our result showed that treatment with sepsis serum can control migration by decrease in CXCR4 level (P ≤ 0.05) compared to control group. Moreover it was also reported that sepsis serum decreased mRNA expression of CXCR4 in MScs. Conclusions: In our study, MSCs treated with septic serum were no longer able to migrate . Probably many variables such as source, dose, injection time, and injection route of MSCs after sepsis induction in the animal models are key factors for successful cell therapy.

Phased Array Beamforming Methods for Powering Biomedical Ultrasonic Implants.

Millimeter-scale implants using ultrasound (US) for power and communication have been proposed for a range of deep-tissue applications, including neural recording and stimulation. However, published implementations have shown high sensitivity to misalignment with the external US transducer. Ultrasonic beamforming using a phased array to these implants can improve tolerance to misalignment, reduce implant volume, and allow multiple implants to be operated simultaneously in different locations. This article details the design of a custom planar phased array US system, which is capable of steering and focusing US power within a 3-D volume. Analysis and simulation is performed to determine the choice of array element pitch, with special attention given to maximizing the power available at the implant while meeting FDA limits for diagnostic US. Time reversal (TR) is proposed as a computationally simple approach to beamforming that is robust despite scattering and inhomogeneity of the acoustic medium. This technique is demonstrated both in active drive and pulse-echo modes, and it is experimentally compared with other beamforming techniques by measuring energy transfer efficiency. Simultaneous power delivery to multiple implants is also demonstrated.

Genetic Diversity Assessment of Iranian Kentucky Bluegrass Accessions: I. ISSR Markers and Their Association with Habitat Suitability Within and Between Different Ecoregions.

Poa pratensis L. is a commonly used cool-season turfgrass and endemic to Iran. This research was carried out to examine the genetic diversity of this plant within and between ecoregions of Iran and the impact of climatic variables and elevation on the distribution of its genotypes, as well as habitat suitability modeling. We used fifty accessions collected from six ecoregions (West, South, North, North-West and North-East) for genetic diversity assessment using 20 ISSR marker primers. The prospective ecoregions for Kentucky bluegrass production were projected using habitat suitability modeling, which took into account important environmental parameters, such as annual mean temperature, annual mean rainfall, and elevation. According to the UPMGA dendrogram, the accessions were divided into two major types and four subclasses. The genetic distance between the North and North-east accessions, as well as the Center accessions, was greater than that of the other genotypes. Center accessions had the greatest levels of polymorphism, effective number of alleles, Shannon index, and Nei's genetic diversity. The FR method was used to create the habitat suitability map based on environmental factors. Rainfall had the largest influence on the genotype distribution of P. pratensis L. The findings of this study can be used as raw materials in future breeding programs to improve and generate new cultivars with superior characteristics. It can also assist programs in identifying rare cultivars as well as preserving and developing native P. pratensis L. genotypes.

Global prevalence of Giardia duodenalis in cattle: A systematic review and meta-analysis.

Giardia duodenalis is an important intestinal parasite responsible for diarrhea in humans and animals worldwide. Up to now, G. duodenalis infections in cattle have been reported in many studies around the world. Hence, the aim of the present study is to report on the distribution of G. duodenalis in cattle at global scale and to evaluate the global prevalence, risk factors and genetic characterization of G. duodenalis infection among cattle worldwide. International databases were systematically searched to identify relevant studies. A random-effects meta-analysis model was used to estimate the overall and the subgroup-pooled prevalence of G. duodenalis across studies, and the variance between studies (heterogeneity) was quantified by I2 index. One hundred and fifty-eight articles (including 195 datasets), from 48 countries met eligibility criteria for analysis. Considering detection methods, the pooled prevalence was estimated to be 24% (95% confidence interval (CI), 19-30%) using copro-antigen techniques, 22% (95% CI, 17-28%) using molecular, and 16% (95% CI, 12-20%) using microscopic detection. Molecular methods showed that the highest number of reports were associated with assemblage E (45/46; 97.83% studies), assemblage A (33/46; 71.74% studies) and assemblage A+E (10/46; 21.74% studies). The pooled prevalence different of subgroups (WHO regions, countries, and type of cattle) were analyzed separately. Moreover, a significant association was observed between G. duodenalis infection with cattle suffering from diarrhea (odds ratio (OR), 2.61; 95% CI, 1.50-4.55) and pre-weaned calves (OR, 1.79; 95% CI, 1.08-2.95). These results suggest that the corresponding control scheme and effective management measures should be formulated to reduce the transmission of G. duodenalis infection according to the difference of geographical conditions in different areas.

Prognostic Value of LncRNA KRT18P55 in Patients with Intestinal Type of Gastric Cancer.

PURPOSE: Gastric cancer (GC) is a heterogeneous disease, and this heterogeneity significantly affects survival and treatment outcomes. Identification of molecular biomarkers specific for early-stage GC can help clinicians to choose more precise and effective treatment approaches. Long non-coding RNAs (lncRNAs) have the potential to be used as biomarkers because of their tissue specificity, stability, and availability in body fluids. In this study, we aimed to investigate changes in the expression levels of lncRNA KRT18P55 and to assess its biomarker potentials in patients with GC. METHODS: Tumor and non-tumor marginal tissues were collected from 102 patients at Noor-Nejat Hospital (Tabriz, Iran). RNA was isolated, and quantitative reverse transcriptase PCR (qRT-PCR) was performed to assess KRT18P55 expression levels in tumor and non-tumor tissue samples. The receiver operating characteristic (ROC) curve analysis was performed to evaluate potentials of KRT18P55 as a prognostic biomarker in GC. SPSS and GraphPad Prism software were used for data analysis. RESULTS: We found that KRT18P55 is significantly overexpressed in tumor as compared to non-tumor tissues (p < 0.0001). We found a significant association between KRT18P55 overexpression and intestinal GC subtype (p < 0.0001), lymph node metastasis (p = 0.013), and Helicobacter pylori infection (p = 0.033). Based on the ROC analysis, KRT18P55 showed a sensitivity and specificity of 53.92% and 77.45%, respectively. CONCLUSION: Overexpression of KRT18P55 in gastric tumors is suggestive of its oncogenic role in GC. In addition, KRT18P55 may be used as a potential prognosis biomarker and therapeutic target in intestinal GC subtype.

Towards an Implantable Fluorescence Image Sensor for Real-Time Monitoring of Immune Response in Cancer Therapy.

Real-time monitoring of cellular-level changes inside the body provides key information regarding disease progression and therapy assessment for critical care including cancer therapy. Current state-of-the-art oncological imaging methods impose unnecessary latencies to detect small cell foci. Invasive methods such as biopsies, on the other hand, cause disruption if deployed on a repeated basis. Therefore, they are not practical for real-time assessments of the tumor tissue. This work presents a proof-of-concept design for an implantable fluorescence lensless image sensor to address the pervasive challenge of real-time tracking of the immune response in immunotherapy. The 2.4x4.7 mm2 integrated circuit (IC) prototype consists of a 36 by 40 pixel array, a laser driver and a power management unit harvesting power and transferring 11.5 kbits/frame through a wireless ultrasound link while implanted 2 cm deep inside the body. Compared to prior art, this is the first full-fledged wireless system implementing chip-scale fluorescence microscopy to the best of our knowledge.Clinical relevance- This prototype can be used to personalize immunotherapy for the 50% of cancer patients who do not initially respond to the therapy.

Interleukin-1 in obesity-related low-grade inflammation: From molecular mechanisms to therapeutic strategies.

Since adipose tissue (AT) can upregulate pro-inflammatory interleukins (ILs) via storing extra lipids in obesity, obesity is considered the leading cause of chronic low-grade inflammation. These ILs can pave the way for the infiltration of immune cells into the AT, ultimately resulting in low-grade inflammation and dysregulation of adipocytes. IL-1, which is divided into two subclasses, i.e., IL-1α and IL-1ß, is a critical pro-inflammatory factor. In obesity, IL-1α and IL-1ß can promote insulin resistance via impairing the function of adipocytes and promoting inflammation. The current study aims to review the detailed molecular mechanisms and the roles of IL-1α and IL-1ß and their antagonist, interleukin-1 receptor antagonist(IL-1Ra), in developing obesity-related inflammatory complications, i.e., type II diabetes (T2D), non-alcoholic steatohepatitis (NASH), atherosclerosis, and cognitive disorders. Besides, the current study discusses the recent advances in natural drugs, synthetic agents, and gene therapy approaches to treat obesity-related inflammatory complications via suppressing IL-1.

In vitro evaluation of cytotoxic effects of di (2-ethylhexyl) phthalate (DEHP) produced by Bacillus velezensis strain RP137 isolated from Persian Gulf.

Phthalates are widely used in polymer science and have potential toxicity related to their chemical structures. However, lots of evidence indicate that phthalate derivatives are undoubtedly produced as secondary metabolites by organisms, including plants, animals, and microorganisms. In the present study, Bacillus velezensis strain RP137 was cultured under optimized conditions. Its biomass was extracted with ethyl acetate with one fraction showing cytotoxic properties. A pure compound was isolated from the active fraction using combined silica gel and LH20 size exclusion column chromatography. Structural evaluation including FT-IR, 1H NMR, 13C NMR, HR-MS and CHN analysis identified the purified compound as di(2-ethylhexyl)phthalate (DEHP) with the formula C24H38O4 and the molecular weight of 389.29 Da. The microorganism-derived (stereospecific) DEHP was strongly reduced the proliferation and induced cytotoxic effects on various eukaryotic cell lines in compare to the synthetic racemic mixture of the compound when assessed by MTT assay. Furthermore, crystal violet assay and morphological changes confirmed the cytotoxic effect of DEHP. Interestingly, non-malignant SV40-immortalized fibroblast cells were less affected by the purified DEHP. Further evaluation on the antibacterial activity of DEHP documented no effect toward Gram-positive (S. aureus) and Gram-negative (E. coli and P. aeruginosa) pathogens even at a high concentration of 100 µM. In conclusion, existence of DEHP as byproduct of microorganism's metabolism can seriously be considered as a warning to human health.

Carbon Nanotubes: Smart Drug/Gene Delivery Carriers.

The unique properties of carbon nanotubes (CNTs) (such as their high surface to volume ratios, enhanced conductivity and strength, biocompatibility, ease of functionalization, optical properties, etc.) have led to their consideration to serve as novel drug and gene delivery carriers. CNTs are effectively taken up by many different cell types through several mechanisms. CNTs have acted as carriers of anticancer molecules (including docetaxel (DTX), doxorubicin (DOX), methotrexate (MTX), paclitaxel (PTX), and gemcitabine (GEM)), anti-inflammatory drugs, osteogenic dexamethasone (DEX) steroids, etc. In addition, the unique optical properties of CNTs have led to their use in a number of platforms for improved photo-therapy. Further, the easy surface functionalization of CNTs has prompted their use to deliver different genes, such as plasmid DNA (PDNA), micro-RNA (miRNA), and small interfering RNA (siRNA) as gene delivery vectors for various diseases such as cancers. However, despite all of these promises, the most important continuous concerns raised by scientists reside in CNT nanotoxicology and the environmental effects of CNTs, mostly because of their non-biodegradable state. Despite a lack of widespread FDA approval, CNTs have been studied for decades and plenty of in vivo and in vitro reports have been published, which are reviewed here. Lastly, this review covers the future research necessary for the field of CNT medicine to grow even further.

The ω-3 endocannabinoid docosahexaenoyl ethanolamide reduces seizure susceptibility in mice by activating cannabinoid type 1 receptors.

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are the most recognized omega-3 unsaturated fatty acids showing neuroprotective activity in animal and clinical studies. Docosahexaenoyl ethanolamide (DHEA) and eicosapentaenoyl ethanolamide (EPEA) are non-oxygenated endogenous metabolites of DHA and EPA, which might be in charge of the anti-seizure activity of the parent molecules. We examined the effect of these metabolites on the threshold of clonic seizures induced by pentylenetetrazole (PTZ). DHEA and EPEA possess similar chemical structure to the endogenous cannabinoids. Therefore, involvement of cannabinoid (CB) receptors in the anti-seizure effect of these metabolites was also investigated. DHA, DHEA, EPEA, AM251 (CB1 receptor antagonist), and AM630 (CB2 receptor antagonist) were administered to mice by intracerebroventricular (i.c.v.) route. Threshold of clonic seizures was determined 10 and/or 15 min thereafter by intravenous infusion of PTZ. The effect of DHA and DHEA on seizure threshold was then determined in mice, which were pretreated with AM251 and/or AM630. DHA (300µM), and DHEA (100 and 300 µM) significantly increased seizure threshold, 15 (p < 0.05) and 10 min (p < 0.01) after administration, respectively. DHEA was more potent than its parent lipid, DHA in decreasing seizure susceptibility. EPEA (300 and 1000 µM) did not change seizure threshold. AM251 fully prevented the increasing effect of DHA and DHEA on seizure threshold (p < 0.05). AM630 did not inhibit the effect of DHA and DHEA on seizure threshold. This is the first report indicating that DHEA but not EPEA, possesses anti-seizure action via activating CB1 receptors. DHEA is more potent than its parent ω-3 fatty acid DHA in diminishing seizure susceptibility.