Toward modulation of the endocannabinoid system for treatment of gastrointestinal disease: FAAHster but not “higher”

Cannabis has been used to treat various afflictions throughout the centuries, including nausea, vomiting, and pain. It has also been used recreationally for its psychotropic properties, which can include a pleasurable ‘high’ feeling and a decrease in anxiety and tension; however, other may experience dysphoria. Changes in cognition and psychomotor performance are also well‐known with cannabis use. In recent years, our understanding of the endocannabinoid system (ECS) has progressed dramatically; the objective of identifying agents which may allow modulation of the ECS without significant psychotropic side effects may be possible. Inhibition of fatty acid amide hydrolase (FAAH), an important enzyme for the degradation of anandamide and other endogenous cannabinoids, is a promising target to achieve this goal. In this issue of Neurogastroenterology and Motility, Fichna and colleagues report on a novel selective FAAH inhibitor, PF‐3845, with potent antinociceptive and antidiarrheal effects in a mouse model. In this context, we briefly review the components of the ECS, discuss pharmacologic targets for indirect cannabinoid receptor stimulation, and describe recent research with cannabinoids for gut disorders.     

Utility of point-of-care ultrasound in patients with suspected diverticulitis in the emergency department

In emergency department (ED) cases with clinically suspected diverticulitis, diagnostic imaging is often needed for diagnostic confirmation, to exclude complications, and to direct patient management. Patients typically undergo a CT scan in the ED; however, in a subset of cases with suspected diverticulitis, point-of-care ultrasound (POCUS) may provide sufficient data to confirm the diagnosis and ascertain a safe plan for outpatient management.We review the main sonographic features of diverticulitis and discuss the diagnostic accuracy and potential benefits of a POCUS First model.     

Effectiveness of stenting and subsequent re-implantation of disconnected pulmonary artery to restore the pulmonary hemodynamics

Introduction::Early intervention in patients with congenitally disconnected pulmonary artery improves long-term outcome.Case presentation::We present 3 cases of...     

Half Metallic Ferromagnetism and Transport Properties of Zinc Chalcogenides ZnX2Se4 (X = Ti,V, Cr) for Spintronic Applications

In ferromagnetic semiconductors, the coupling of magnetic ordering with semiconductor character accelerates the quantum computing. The structural stability, Curie temperature (T_c), spin polarization, half magnetic ferromagnetism and transport properties of ZnX₂Se₄ (X = Ti, V, Cr) chalcogenides for spintronic and thermoelectric applications are studied here by density functional theory (DFT). The highest value of T_c is perceived for ZnCr₂Se₄. The band structures in both spin channels confirmed half metallic ferromagnetic behavior, which is approved by integer magnetic moments (2, 3, 4) μ_B of Ti, V and Cr based spinels. The HM behavior is further measured by computing crystal field energy ΔE _crystal, exchange energies Δ _x(d), Δ _x (pd) and exchange constants (N_o α and N_o β ). The thermoelectric properties are addressed in terms of electrical conductivity, thermal conductivity, Seebeck coefficient and power factor in within a temperature range 0–400 K. The positive Seebeck coefficient shows p-type character and the PF is highest for ZnTi2Se4 (1.2 × 10¹¹ W/mK²) among studied compounds.     

Kaempferol suppresses acetaminophen-induced liver damage by upregulation/activation of SIRT1

ContextKaempferol, a flavonoid glycoside, has many hepatoprotective effects in several animals due to its antioxidant potential.ObjectiveThis study evaluated the hepatoprotective effect of kaempferol against acetaminophen (APAP)-induced liver damage and examined whether the protection involved modulation of silent information regulator 1 (SIRT1) signalling.Materials and methodsAdult male Wistar rats were classified into four groups (n = 8) and treated as follows: control + normal saline (vehicle), control + kaempferol (250 mg/kg), APAP (800 mg/kg, a single dose) and APAP + kaempferol. Kaempferol was administered for the first seven days followed by administration of APAP. The study was ended 24 h after APAP administration.ResultsAt the histological level, kaempferol reduced liver damage in APAP-treated rats. It also reduced the hepatic levels of TNF-α (66.3%), IL-6 (38.6%) and protein levels of caspase-3 (88.2%), and attenuated the increase in circulatory serum levels of ALT (47.6%), AST (55.8%) and γ-GT (35.2%) in APAP-treated rats. In both the controls and APAP-treated rats, kaempferol significantly increased the hepatic levels of glutathione (GSH) and superoxide dismutase, suppressed MDA and reactive oxygen species (ROS) levels, increased protein levels of Bcl-2 and downregulated protein levels of Bax and cleaved Bax. Concomitantly, it reduced the expression of CYP2E1, and the activity and protein levels of SIRT1. Consequently, it decreased the acetylation of all SIRT1 targets including PARP1, p53, NF-κB, FOXO-1 and p53 that mediate antioxidant, anti-inflammatory and anti-apoptotic effects.Discussion and conclusionsThis study encourages the use of kaempferol in further clinical trials to treat APAP-induced hepatotoxicity.     

Designing a novel visible-light-driven heterostructure Ni–ZnO/S-g-C3N4 photocatalyst for coloured pollutant degradation

In this study, photocorrosion of ZnO is inhibited by doping Ni in the ZnO nanostructure and electron–hole recombination was solved by forming a heterostructure with S-g-C₃N₄. Ni is doped into ZnO NPs from 0 to 10% (w/w). Among the Ni-decorated ZnO NPs, 4% Ni-doped ZnO NPs (4NZO) showed the best performance. So, 4% Ni–ZnO was used to form heterostructure NCs with S-g-C₃N₄. NZO NPs were formed by the wet co-precipitation route by varying the weight percentage of Ni (0–10% w/w). Methylene blue (MB) was used as a model dye for photocatalytic studies. For the preparation of the 4NZO-x-SCN nanocomposite, 4NZO NPs were formed in situ in the presence of various concentrations of S-g-C₃N₄ (10–50% (w/w)) by using the coprecipitation route. The electron spin resonance (ESR) and radical scavenger studies showed that O₂⁻ and OH free radicals were the main reactive species that were responsible for MB photodegradation.

Ni-doped ZnO/S-g-C₃N₄ nanocomposites were formed as a novel heterostructure photocatalyst.     

Design,synthesis, docking study and anticancer evaluation of new trimethoxyphenyl pyridine derivatives as tubulin inhibitors and apoptosis inducers

Microtubules have become an appealing target for anticancer drug development including mainly colchicine binding site inhibitors (CBSIs). A new series of novel trimethoxypyridine derivatives were designed and synthesized as tubulin targeting agents. In vitro anti-proliferative activities of the tested compounds compared to colchicine against hepatocellular carcinoma (HepG-2), colorectal carcinoma (HCT-116), and breast cancer (MCF-7) was carried out. Most of compounds showed significant cytotoxic activities. Compounds Vb, Vc, Vf, Vj and VI showed superior anti-proliferative activities to colchicine. Where compound VI showed IC₅₀ values of 4.83, 3.25 and 6.11 μM compared to colchicine (7.40, 9.32, 10.41 μM) against HCT 116, HepG-2 and MCF-7, respectively. The enzymatic activity against tubulin enzyme was carried out for the compounds that showed high anti-proliferative activity. Also, compound VI exhibited the highest tubulin polymerization inhibitory effect with an IC₅₀ value of 8.92 nM compared to colchicine (IC₅₀ value = 9.85 nM). Compounds Vb, Vc, Vf, Vj, & VIIIb showed promising activities with IC₅₀ values of 22.41, 17.64, 20.39, 10.75, 31.86 nM, respectively. Cell cycle and apoptosis test for compound VI against HepG-2 cells, indicated that compound VI can arrest cell cycle at G2/M phase, and can cause apoptosis at pre-G1 phase, with high apoptotic effect 18.53%. Molecular docking studies of the designed compounds confirmed the essential hydrogen bonding with CYS241 beside the hydrophobic interaction at the binding site compared to reference compounds which assisted in the prediction of the structure requirements for the detected antitumor activity.

Interaction of compounds VI (IC₅₀ = 8.92 nM) (A) and Vj (IC₅₀ = 10.75 nM) (B) with key amino acids of CBS.     

Fabrication and Characterization of Highly Efficient As-Synthesized WO3/Graphitic-C3N4 Nanocomposite for Photocatalytic Degradation of Organic Compounds

The incorporation of tungsten trioxide (WO₃) by various concentrations of graphitic carbon nitride (g-C₃N₄) was successfully studied. X-ray diffraction (XRD), Scanning Electron Microscope (SEM), and Diffused Reflectance UV-Vis techniques were applied to investigate morphological and microstructure analysis, diffused reflectance optical properties, and photocatalysis measurements of WO₃/g-C₃N₄ photocatalyst composite organic compounds. The photocatalytic activity of incorporating WO3 into g-C₃N₄ composite organic compounds was evaluated by the photodegradation of both Methylene Blue (MB) dye and phenol under visible-light irradiation. Due to the high purity of the studied heterojunction composite series, no observed diffraction peaks appeared when incorporating WO₃ into g-C₃N₄ composite organic compounds. The particle size of the prepared composite organic compound photocatalysts revealed no evident influence through the increase in WO₃ atoms from the SEM characteristic. The direct and indirect bandgap were recorded for different mole ratios of WO₃/g-C₃N_4, and indicated no apparent impact on bandgap energy with increasing WO₃ content in the composite photocatalyst. The composite photocatalysts’ properties better understand their photocatalytic activity degradations. The pseudo-first-order reaction constants (K) can be calculated by examining the kinetic photocatalytic activity.