Molecular screening of phytocompounds targeting the interface between influenza A NS1 and TRIM25 to enhance host immune responses.

BACKGROUND: Influenza A virus causes severe respiratory illnesses, especially in developing nations where most child deaths under 5 occur due to lower respiratory tract infections. The RIG-I protein acts as a sensor for viral dsRNA, triggering interferon production through K63-linked poly-ubiquitin chains synthesized by TRIM25. However, the influenza A virus's NS1 protein hinders this process by binding to TRIM25, disrupting its association with RIG-I and preventing downstream interferon signalling, contributing to the virus's evasion of the immune response. METHODS: In our study we used structural-based drug designing, molecular simulation, and binding free energy approaches to identify the potent phytocompounds from various natural product databases (>100,000 compounds) able to inhibit the binding of NS1 with the TRIM25. RESULTS: The molecular screening identified EA-8411902 and EA-19951545 from East African Natural Products Database, NA-390261 and NA-71 from North African Natural Products Database, SA-65230 and SA- 4477104 from South African Natural Compounds Database, NEA- 361 and NEA- 4524784 from North-East African Natural Products Database, TCM-4444713 and TCM-6056 from Traditional Chinese Medicines Database as top hits. The molecular docking and binding free energies results revealed that these compounds have high affinity with the specific active site residues (Leu95, Ser99, and Tyr89) involved in the interaction with TRIM25. Additionally, analysis of structural dynamics, binding free energy, and dissociation constants demonstrates a notably stronger binding affinity of these compounds with the NS1 protein. Moreover, all selected compounds exhibit exceptional ADMET properties, including high water solubility, gastrointestinal absorption, and an absence of hepatotoxicity, while adhering to Lipinski's rule. CONCLUSION: Our molecular simulation findings highlight that the identified compounds demonstrate high affinity for specific active site residues involved in the NS1-TRIM25 interaction, exhibit exceptional ADMET properties, and adhere to drug-likeness criteria, thus presenting promising candidates for further development as antiviral agents against influenza A virus infections.

Exploring bi-carbazole-linked triazoles as inhibitors of prolyl endo peptidase via integrated in vitro and in silico study.

A serine protease called prolyl endopeptidase (PEP) hydrolyses the peptide bonds on the carboxy side of the proline ring. The excessive PEP expression in brain results in neurodegenerative illnesses like dementia, Alzheimer's disease, and Parkinson's disease. Results of the prior studies on antioxidant activity, and the non-cytotoxic effect of bi-carbazole-linked triazoles, encouraged us to extend our studies towards its anti-diabetic potential. Hence, for this purpose all compounds 1-9 were evaluated to reveal their anti-prolyl endo peptidase activity. Fortunately, seven compounds resulted into significant inhibitory capability ranging from 26 to 63 µM. Among them six compounds 4-9 exhibited more potent inhibitory activity with IC50 values 46.10 ± 1.16, 42.30 ± 1.18, 37.14 ± 1.21, 26.29 ± 0.76, 28.31 ± 0.64 and 31.11 ± 0.84 µM respectively, while compound 3 was the least active compound in the series with IC50 value 63.10 ± 1.58 µM comparing with standard PEP inhibitor bacitracin (IC50 = 125 ± 1.50 µM). Moreover, mechanistic study was performed for the most active compounds 7 and 8 with Ki values 24.10 ± 0.0076 and 23.67 ± 0.0084 µM respectively. Further, the in silico studies suggested that the compounds exhibited potential interactions and significant molecular conformations, thereby elucidating the structural basis for their inhibitory effects.

Unraveling the mechanisms of Sofosbuvir resistance in HCV NS3/4A protease: Structural and molecular simulation-based insights.

Current management of HCV infection is based on Direct-Acting Antiviral Drugs (DAAs). However, resistance-associated mutations, especially in the NS3 and NS5B regions are gradually decreasing the efficacy of DAAs. Among the most effective HCV NS3/4A protease drugs, Sofosbuvir also develops resistance due to mutations in the NS3 and NS5B regions. Four mutations at positions A156Y, L36P, Q41H, and Q80K are classified as high-level resistance mutations. The resistance mechanism of HCV NS3/4A protease toward Sofosbuvir caused by these mutations is still unclear, as there is less information available regarding the structural and functional effects of the mutations against Sofosbuvir. In this work, we combined molecular dynamics simulation, molecular mechanics/Generalized-Born surface area calculation, principal component analysis, and free energy landscape analysis to explore the resistance mechanism of HCV NS3/4A protease due to these mutations, as well as compare interaction changes in wild-type. Subsequently, we identified that the mutant form of HCV NS3/4A protease affects the activity of Sofosbuvir. In this study, the resistance mechanism of Sofosbuvir at the atomic level is proposed. The proposed drug-resistance mechanism will provide valuable guidance for the design of HCV drugs.

Identification of IL-2 inducible tyrosine kinase inhibitors by quantum mechanics and ligand based virtual screening approaches.

Interleukin-2-inducible T-cell kinase (ITK) is a crucial intracellular signaling mediator in normal and malignant T-cells and natural killer cells. Selective inhibition of ITK might be useful for treating a variety of disorders including; autoimmune, inflammatory, and neoplastic disorders. Over the past two decades, the clinical management of ITK inhibitors has progressed dramatically. So far, specific inhibitor with no off-target effects against ITK is available. Herein, we aim to discover potential virtual hits to fasten the process of drug design and development against ITK. In this regard, the key chemical characteristics of ITK inhibitors were identified using ligand-based pharmacophore modeling. The validated pharmacophore comprises one hydrogen bond donor and three hydrogen bond acceptors and was utilized as a 3D query in virtual screening using ZINC, Covalent, and in-house databases. A total of 12 hit compounds were chosen on the basis of their critical interactions with the significant amino acids of ITK. The orbital energies such as HOMO and LUMO of the hit compounds were calculated to evaluate the inhibitor's potencies. Further, molecular dynamics simulation demonstrated the stability of ITK upon binding of selected virtual hits. Binding energy using the MMGBSA method showed the potential binding affinity of all the hits with ITK. The research identifies key chemical characteristics with geometric restrictions that lead to ITK inhibition.Communicated by Ramaswamy H. Sarma.

Hemagglutinin 3 and 8 can be the most efficient influenza subtypes for human host invasion; a comparative in silico approach.

The severity of the influenza virus infection is largely determined by its ability to invade the human host receptor. This critical step is conducted by utilizing hemagglutinin (HA) due to its binding with sialic acid 2,6 (SA). Though 18 subtypes (H1-H18) of HA have been identified, the most efficient one for conducting the host entry has not yet been resolved. This study aims to assess the severity of infections for HA variants by conducting a comparative docking of H1-H18 with the human SA receptor. Eighteen viral 3D structures were retrieved, minimized, and optimized for docking with human SA. In all retrieved structures, five conserved amino acid residues were selected for docking with human SA. Special protein grids were prepared by locating these five residues in the 18 selected subtypes. Results showed that H3 and H8 exerted the highest standard precision and extra precision docking scores, and the highest binding affinities with the human SA, respectively. Phylogenetic analyses confirmed the actual positioning of the selected 3D structures and showed these docked structures belonged to their usual classes due to the extremely close distances found in each docked subtype compared with its corresponding non-docked structures. H8-SA showed slightly better RMSD and SASA values than H3-SA, while H3-SIA showed more favourable radius of gyration scores than H8-SIA in the majority of the simulation period. Due to the highest affinity of binding of H3 and H8 with the human receptor, special caution should be exercised regarding any possible outbreak mediated by these subtypes in human populations. However, it is important to acknowledge a limitation inherent to the computational approach; it may hold relative rather than absolute significance. Further research is needed to deepen our understanding of the intricate interplay between HA variants and the host receptor, taking into account the broader context of viral infection dynamics.Communicated by Ramaswamy H. Sarma.

Masoprocol: a promising candidate for targeting insulin resistance by inhibiting resistin with optimal druglikeness Potentials: an in silico approach.

Resistin is a cysteine-rich secretory hormone that induces resistance to insulin, and its elevated expression is correlated with the onset of diabetes and several related metabolic disorders. Resistin performs its inhibitory role by connecting three identical subunits through Cys22-based disulfide linkages. The necessity to inhibit the formation of resistin trimer is one of the essential means to prevent the aggravation of diabetes mellitus type 2, obesity, and atherosclerosis. This study was conducted to screen the clinically approved drugs to find the most potent one to inhibit resistin with the best pharmacokinetics and drug-likeness properties. A total of 4654 clinically approved drugs were docked against the Cys22 residue of resistin. The top ten drugs with the highest high-precision (XP) docking scores were selected. Ioversol and masoprocol showed the highest XP docking and Molecular Mechanics-Generalized Born Surface Area (MMGBSA) scores, respectively, with double hydrogen bonding with the targeted Cys22. Molecular dynamics (MD) simulations showed that the masoprocol-resistin complex exhibited lower root mean square deviation (RMSD), radius of gyration, and root mean square fluctuation (RMSF) values than those observed in the ioversol-resistin complex. Both drugs induced drastic conformational changes in resistin monomer interactions. However, ioversol did not prove satisfying drug-likeness properties, while masoprocol showed the most favourable pharmacokinetic and drug-likeness properties. This study has demonstrated that masoprocol offers a novel inhibitory effect on resistin with the highest ligand affinity, making it a promising drug for combating insulin resistance.Communicated by Ramaswamy H. Sarma.

Design of a novel multiple epitope-based vaccine: an immunoinformatics approach to combat monkeypox.

Monkeypox virus is an infectious agent that causes fever, Pneumonitis encephalitis, rash, lymphadenopathy and bacterial infection. The current outbreak of monkeypox has reawakened the global health concern. In the current situation of increasing viral infection, no vaccine or drug is available for monkeypox. Thus, there is an urgent need for viable vaccine development to prevent viral transmission by boosting human immunity. Herein, using immunoinformatics approaches, a multi-epitope vaccine was constructed for the Monkeypox virus. In this connection, B-Cell and T-cell epitopes were identified and joined with the help of adjutants and linkers. The vaccine construct was selected based on promising vaccine candidates and immunogenic potential. Further epitopes were selected based on antigenicity score, non-allergenicity and good immunological properties. Molecular docking reveals strong interactions between TLR-9 and the predicted vaccine construct. Finally, molecular dynamics simulations were performed to evaluate the stability and compactness of the constructed vaccine. The MD simulation results demonstrated the significant stability of the polypeptide vaccine construct. The predicted vaccine represented good stability, expression, immunostimulatory capabilities and significant solubility. Design vaccine was verified as efficient in different computer-based immune response investigations. Additionally, the constructed vaccine also represents a good population coverage in computer base analysis.Communicated by Ramaswamy H. Sarma.

Levetiracetam ameliorates epileptogenesis by modulating the adenosinergic pathway in a kindling model of epilepsy in mice.

Background: Levetiracetam (LEV) has been found to have an antihyperalgesic effect via acting on the adenosine system. However, the effects of LEV on the modulation of the adenosine system in the brain have not been elucidated in the prevention of seizures and epilepsy. The present study aimed to explore the possible LEV mechanisms of action in the adenosine signaling systems in an animal model of epilepsy. Methodology: A docking study was initially performed to determine the possible interaction of LEV with adenosine A1 receptors (A1Rs) and equilibrative nucleoside transporters-1 (ENT1). The experimental study was divided into an acute seizure test (32 mice distributed into 4 groups) and a chronic kindling model study (40 mice distributed into 5 groups), followed by gene expression analysis and immunohistochemistry. The kindling model lasted 26 days and took 13 subconvulsive doses of pentylenetetrazole (PTZ) to completely kindle the mice in the PTZ control group. Gene expression changes in the A1Rs, potassium inwardly-rectifying channel 3.2 (Kir3.2), and ENT1 in the brain tissue samples of the mice following treatment with LEV were analyzed using reverse transcription-quantitative polymerase chain reaction, and immunohistochemistry was performed for the A1R protein expression. Results: Docking studies predicted a significant interaction of LEV with A1Rs and ENT1 proteins. Results from the acute testing revealed that caffeine (100 mg/kg) and 8-cyclopentyl-1,3-dipropylxanthine (25 mg/kg) significantly reversed the antiseizure effects of LEV by reversing the percent protection and shortening the onset of the first myoclonic jerk (FMJ) and generalized clonic seizures (GCSs). In the PTZ-induced kindling, LEV demonstrated an increased gene expression of A1Rs and Kir3.2 in the brain. LEV also significantly reduced the gene expression of ENT1. Furthermore, the immunohistochemical analysis showed that LEV increased the protein expression of A1Rs in the brain. Conclusion: Based on these results, it can be concluded that LEV modulates epileptogenesis by acting on the adenosine pathway in the central nervous system.

Cheminformatics-Based Discovery of Potential Chemical Probe Inhibitors of Omicron Spike Protein.

During the past two decades, the world has witnessed the emergence of various SARS-CoV-2 variants with distinct mutational profiles influencing the global health, economy, and clinical aspects of the COVID-19 pandemic. These variants or mutants have raised major concerns regarding the protection provided by neutralizing monoclonal antibodies and vaccination, rates of virus transmission, and/or the risk of reinfection. The newly emerged Omicron, a genetically distinct lineage of SARS-CoV-2, continues its spread in the face of rising vaccine-induced immunity while maintaining its replication fitness. Efforts have been made to improve the therapeutic interventions and the FDA has issued Emergency Use Authorization for a few monoclonal antibodies and drug treatments for COVID-19. However, the current situation of rapidly spreading Omicron and its lineages demands the need for effective therapeutic interventions to reduce the COVID-19 pandemic. Several experimental studies have indicated that the FDA-approved monoclonal antibodies are less effective than antiviral drugs against the Omicron variant. Thus, in this study, we aim to identify antiviral compounds against the Spike protein of Omicron, which binds to the human angiotensin-converting enzyme 2 (ACE2) receptor and facilitates virus invasion. Initially, docking-based virtual screening of the in-house database was performed to extract the potential hit compounds against the Spike protein. The obtained hits were optimized by DFT calculations to determine the electronic properties and molecular reactivity of the compounds. Further, MD simulation studies were carried out to evaluate the dynamics of protein-ligand interactions at an atomistic level in a time-dependent manner. Collectively, five compounds (AKS-01, AKS-02, AKS-03, AKS-04, and AKS-05) with diverse scaffolds were identified as potential hits against the Spike protein of Omicron. Our study paves the way for further in vitro and in vivo studies.

Deciphering the Impact of Mutations on the Binding Efficacy of SARS-CoV-2 Omicron and Delta Variants With Human ACE2 Receptor.

The pandemic of COVID-19, caused by SARS-CoV-2, has globally affected the human health and economy. Since the emergence of the novel coronavirus SARS-CoV-2, the life-threatening virus continues to mutate and evolve. Irrespective of acquired natural immunity and vaccine-induced immunity, the emerging multiple variants are growing exponentially, crossing the territorial barriers of the modern world. The rapid emergence of SARS-CoV-2 multiple variants challenges global researchers regarding the efficacy of available vaccines and variant transmissibility. SARS-CoV-2 surface-anchored S-protein recognizes and interacts with the host-cell ACE2, facilitating viral adherence and entrance into the cell. Understanding the interfacial interactions between the spike protein of SARS-CoV-2 variants and human ACE2 receptor is important for the design and development of antiviral therapeutics against SARS-CoV-2 emerging variants. Despite extensive research, the crucial determinants related to the molecular interactions between the spike protein of SARS-CoV-2 variants and host receptors are poorly understood. Thus, in this study, we explore the comparative interfacial binding pattern of SARS-CoV-2 spike RBD of wild type, Delta, and Omicron with the human ACE2 receptor to determine the crucial determinants at the atomistic level, using MD simulation and MM/GBSA energy calculations. Based on our findings, the substitution of Q493R, G496S, Q498R, and Y505H induced internal conformational changes in Omicron spike RBD, which leads to higher binding affinity than Delta spike RBD with the human ACE2 receptor, eventually contributing to higher transmission and infectivity. Taken together, these results could be used for the structure-based design of effective antiviral therapeutics against SARS-CoV-2 variants.

Immunoinformatic approach for the construction of multi-epitopes vaccine against omicron COVID-19 variant.

The newly discovered SARS-CoV-2 Omicron variant B.1.1.529 is a Variant of Concern (VOC) announced by the World Health Organization (WHO). It's becoming increasingly difficult to keep these variants from spreading over the planet. The fifth wave has begun in several countries because of Omicron variant, and it is posing a threat to human civilization. As a result, we need effective vaccination that can tackle Omicron SARS-CoV-2 variants that are bound to emerge. Therefore, the current study is an initiative to design a peptide-based chimeric vaccine that may potentially battle SARS-CoV-2 Omicron variant. As a result, the most relevant epitopes present in the mutagenic areas of Omicron spike protein were identified using a set of computational tools and immunoinformatic techniques to uncover common MHC-1, MHC-II, and B cell epitopes that may have the ability to influence the host immune mechanism. A final of three epitopes from CD8+ T-cell, CD4+ T-cell epitopes, and B-cell were shortlisted from spike protein, and that are highly antigenic, IFN-γ inducer, as well as overlapping for the construction of twelve vaccine models. As a result, the antigenic epitopes were coupled with a flexible and stable peptide linker, and the adjuvant was added at the N-terminal end to create a unique vaccine candidate. The structure of a 3D vaccine candidate was refined, and its quality was assessed by using web servers. However, the applied immunoinformatic study along with the molecular docking and simulation of 12 modeled vaccines constructs against six distinct HLAs, and TLRs (TLR2, and TLR4) complexes revealed that the V1 construct was non-allergenic, non-toxic, highly immunogenic, antigenic, and most stable. The vaccine candidate's stability was confirmed by molecular dynamics investigations. Finally, we studied the expression of the suggested vaccination using codon optimization and in-silico cloning. The current study proposed V1 Multi-Epitope Vaccine (MEV) as a significant vaccine candidate that may help the scientific community to treat SARS-CoV-2 infections.

Theoretical investigation of selective ligand binding mode of galanin receptors.

The Galaninergic system consist of Galanin and its receptors, involved in neuromodulation and neurotransmission. Galanin regulate its physiologic and pathologic functions by interacting with three G-protein coupled receptors; GalR1, GalR2 and GalR3. The widespread distribution of Galanin and its receptor subtypes in central and peripheral nervous system makes them an attractive drug target for the treatment of neurological diseases. However, subtypes selective ligands paucity and little structural information related to either Galanin receptors and Galanin receptor-ligand complexes hampered the structure-based drug design. Thus computational modeling characterization strategy was utilized for Galanin receptor 3D structure prediction and subtypes ligands binding selectivity. Reported ligands with experimental activity were docked against the homology model of Galanin receptors. Further, the MD simulation and binding free energy calculation were carried out to determine the binding interactions pattern consistency and selectivity towards receptor subtype. Results of binding free energy of per residue indicate key contribution of GalR1 Phe115 and His267 in the selective binding of ligands while Tyr103, Tyr270 and His277 play major role in the selective binding of GalR3 ligands. Our study provide rationale for further in silico virtual screening of small molecules for the development of selective ligands against Galanin receptor subtypes.Communicated by Ramaswamy H. Sarma.

Probing CAS database as prospective antiviral agents against SARS-CoV-2 main protease.

The pandemic of COVID-19 has an unprecedented impact on global health and economy. The novel SARS-CoV-2 is recognized as the etiological agent of current outbreak. Because of its contagious human-to-human transmission, it is an utmost global health emergency at present. To mitigate this threat many scientists and researchers are racing to develop antiviral therapy against the virus. Unfortunately, to date no vaccine or antiviral therapeutic is approved thus there is an urgent need to discover antiviral agent to help the individual who are at high risk. Virus main protease or chymotrypsin-like protease plays a pivotal role in virus replication and transcription; thus, it is considered as an attractive drug target to combat the COVID-19. In this study, multistep structure based virtual screening of CAS antiviral database is performed for the identification of potent and effective small molecule inhibitors against chymotrypsin-like protease of SARS-CoV-2. Consensus scoring strategy combine with flexible docking is used to extract potential hits. As a result of extensive virtual screening, 4 hits were shortlisted for MD simulation to study their stability and dynamic behavior. Insight binding modes demonstrated that the selected hits stabilized inside the binding pocket of the target protein and exhibit complementarity with the active site residues. Our study provides compounds for further in vitro and in vivo studies against SARS-CoV-2.

Luminal-apposing stents for benign intraluminal strictures: a large United States multicenter study of clinical outcomes.

BACKGROUND: The use of fully covered lumen-apposing metal stents (LAMS) for benign short gastrointestinal (GI) strictures has been reported. This study aimed to evaluate the safety and efficacy of LAMS for refractory GI strictures. METHODS: A retrospective analysis was performed of patients who underwent LAMS placement for benign GI strictures in 8 United States centers. The primary outcomes were technical success and initial clinical response. Secondary outcomes were reintervention rate and adverse events. RESULTS: A total of 51 patients underwent 61 LAMS placement procedures; 33 (64.7%) had failed previous treatments. The most common stricture location was the pylorus (n=17 patients). Various sizes of stents were used, with 15-mm LAMS placed in 45 procedures, 20-mm LAMS in 14 procedures, and 10-mm LAMS in 2 procedures. The overall technical success, short-term clinical response and reintervention rate after stent removal were 100%, 91.8% and 31.1%, respectively. Adverse events were reported in 17 (27.9%) procedures, with stent migration being the most common (13.1%). In subgroup analysis, both 15 mm and 20 mm stents had comparable short-term clinical response and adverse event rates. However, stent migration (15.6%) was the most common adverse event with 15-mm LAMS while pain (14.3%) was the most common with 20-mm LAMS. The reintervention rate was 80% at 200-day follow up after stent removal. CONCLUSIONS: Using LAMS for treatment of short benign GI strictures is safe and effective. Larger LAMS, such as the new 20 mm in diameter, may have a lower stent migration rate compared to smaller diameter LAMS.

Identification of chymotrypsin-like protease inhibitors of SARS-CoV-2 via integrated computational approach.

Recently, the world has witnessed outbreak of a novel Coronavirus (SARS-CoV-2), the virus which initially emerged in Wuhan, China has now made its way to a large part of the world, resulting in a public emergency of international concern. The functional importance of Chymotrypsin-like protease (3CLpro) in viral replication and maturation turns it into an attractive target for the development of effective antiviral drugs against SARS and other coronaviruses. At present, there is no standard drug regime nor any vaccine available against the infection. The rapid development and identification of efficient interventions against SARS-CoV-2 remains a major challenge. Based on the available knowledge of closely related coronavirus and their safety profiles, repurposing of existing antiviral drugs and screening of available databases is considered a near term strategic and economic way to contain the SARS-CoV-2 pandemic. Herein, we applied computational drug design methods to identify Chymotrypsin-like protease inhibitors from FDA approved antiviral drugs and our in-house database of natural and drug-like compounds of synthetic origin. As a result three FDA approved drugs (Remdesivir, Saquinavir and Darunavir) and two natural compounds (. flavone and coumarine derivatives) were identified as promising hits. Further, MD simulation and binding free energy calculations were performed to evaluate the dynamic behavior, stability of protein-ligand contact, and binding affinity of the hit compounds. Our results indicate that the identified compounds can inhibit the function of Chymotrypsin-like protease (3CLpro) of Coronavirus. Considering the severity of the spread of coronavirus, the current study is in-line with the concept of finding the new inhibitors against the vital pathway of the corona virus to expedite the process of drug discovery.Communicated by Ramaswamy H. Sarma.

Primary Colonic Lymphoma With Paraneoplastic Hypercalcemia.

Primary colonic lymphoma is a rare tumor accounting for 0.1%-0.5% of all colorectal malignancies. We describe a 63-year-old man whose initial presentation was altered mental status due to hypercalcemia. Physical examination revealed a hard, right-sided abdominal mass. Abdominal computed tomography showed a mass in the ascending colon, which on further evaluation with colonoscopy and biopsy was diagnosed as diffuse large B-cell lymphoma. A diagnosis of primary colonic lymphoma was made based on the Dawson criteria, after ruling out any extracolonic involvement. Workup for hypercalcemia showed elevated calcitriol levels, which is a paraneoplastic manifestation of the lymphoma.

Role of cannabis in inflammatory bowel diseases.

For many centuries, cannabis (marijuana) has been used for both recreational and medicinal purposes. Currently, there are about 192 million cannabis users worldwide, constituting approximately 3.9% of the global population. Cannabis comprises more than 70 aromatic hydrocarbon compounds known as cannabinoids. Endogenous circulating cannabinoids, or endocannabinoids, such as anandamide and 2-arachidonoyl-glycerol, their metabolizing enzymes (fatty acid amide hydrolase and monoacylglycerol lipase) and 2 G-protein coupled cannabinoid receptors, CB1 and CB2, together represent the endocannabinoid system and are present throughout the human body. In the gastrointestinal (GI) tract, the activated endocannabinoid system reduces gut motility, intestinal secretion and epithelial permeability, and induces inflammatory leukocyte recruitment and immune modulation through the cannabinoid receptors present in the enteric nervous and immune systems. Because of the effects of cannabinoids on the GI tract, attempts have been made to investigate their medicinal properties, particularly for GI disorders such as pancreatitis, hepatitis, and inflammatory bowel diseases (IBD). The effects of cannabis on IBD have been elucidated in several small observational and placebo-controlled studies, but with varied results. The small sample size and short follow-up duration in these studies make it difficult to show the clear benefits of cannabis in IBD. However, cannabis is now being considered as a potential drug for inflammatory GI conditions, particularly IBD, because of its spreading legalization in the United States and other countries and the growing trend in its use. More high-quality controlled studies are warranted to elucidate the mechanism and benefits of cannabis use as a possible option in IBD management.

Structure Analysis and Ferroelectric Response of Bi0.5Na0.5TiO3 Nanopowder Synthesized by Sol-Gel Method.

In this work, bismuth sodium titanate, Bi0.5±xNa0.5±yTiO3 (BNT, x, y = -0.05-0.08) nanopowders were produced using the low-temperature sol-gel technique. The effects of deficient and excess amounts of Bi and Na on BNT structure were systemically examined through X-ray powder diffraction (XRD), energy dispersive analysis (EDS) and scanning electron microscope (SEM). The optimized composition of the BNT nanopowder was pelletized and sintered at different temperatures (950°C-1150 °C). Highly dense ceramics possessing pure perovskite phase was observed for the sample sintered at an optimum sintering temperature (1100 °C). The ferroelectric properties were found to increase with an increase in sintering temperature up to 1100 °C and then decrease. This study justifies that Bi and Na non-stoichiometry (proper excess), processing and sintering temperatures play important role in the successful synthesis of BNT ceramics.