Search

Zinc cobalt oxide nanostructures were synthesized by electrochemical deposition of zinccobalt alloy at various bath temperatures (15, 30, 45 and 60 °C) and its hydrothermal oxidation at 100 °C. X-ray diffraction pattern and Raman spectroscopy data reveals the formation of spinal structure of ZnCo2O4. Photoluminescence spectra of the samples exhibit broad peaks with a red shift in the emission energy. Diffused reflectance spectroscopy measured the band gap of the synthesized materials; band gap is 3.06, 3.03, 3.02 and 2.99 eV, for samples electrodeposited at 15, 30, 45 and 60 °C, respectively. Optical conductivity of synthesized materials decreases with increasing deposition layers while reflectance shows opposite trend. Thermoelectric set up measures the change in potential difference through synthesized materials when different temperatures are applied and an increment in potential were observed. Seebeck co-efficient and power factor are also studied as function of bath temperature. [ABSTRACT FROM AUTHOR]

The anticancer mediators claim their activity in liquid form as a biocompatible and use in bios stems, which are mostly collected in fluid form. Control on the stability of metal oxide nanoparticles in parallel reducing the effect of large amount on their biological and cytotoxicity activities, remains a challenge. Here anticancer activity and cytotoxicity zinc oxide nanoparticles (NPs) have been presented that are coated with folic acid (F.A) and polyethylene glycol (PEG). The nanoparticles were synthesized by wet chemical method and characterized by x-ray diffraction; scanning electron microscopy and Fourier transform infrared spectroscopy. The cytotoxicity studies were performed on HepG2 cells.MMT assay was used to check the cell viability. The PEG and F.A capped ZnO NPs have shown reduction in cytotoxicity as compare to bare ZnO nanoparticles. [ABSTRACT FROM AUTHOR]

The three samples of SnS with different molarity 1ml, 0.5ml and 0.25ml were prepared by hydrothermal method. The prepared samples were characterized by XRD, SEM and impedance spectroscopies. XRD confirmed the cubic and orthorhombic structure of SnS. The average size of nanoparticles was noted to be about 12.77 nm, 16.43 nm and 16.44 nm at 140 °C. These nanoparticles were of cubic and orthorhombic forms. Average strain came out to be 0.215, 0.142 and 0.140. This result shows that by changing molarity, crystal structure of SnS can be changed. Crystallite size is increasing with decreasing molarity while strain is decreasing. Scanning electron microscopy (SEM) was carried out in order to study sheet like morphology of the samples. The carried-out process showed that the produced sample shows ball resembling spherical form. On the other hand, the frequency distribution and calculation of mean size of SnS nanoparticles, histogram and Gaussian curve were drawn and analyzed. Size range of nano-particles for sample 1ml, 0.5ml and 0.25ml was between (10-65) nm, (20-120) nm, (10-90) nm, respectively. The real part of impedance Z' got maximum value of 0.173 MΩ, 0.31 MΩ, and 0.40 MΩ at three different molarities. Maximum values of imaginary impedance observed were 0.053 MΩ (1ml), 0.112 MΩ (0.5ml) and 0.14 MΩ at different Debye relaxation peaks. The results show that reduction in the molarity increases the impedance and decreases the capacitance. [ABSTRACT FROM AUTHOR]

Objective. Signal denoising methods based on deep learning have been extensively adopted on electroencephalogram devices. However, they are unable to deploy on edge-based portable or wearable (P/W) electronics due to the high computational complexity of the existed models. To overcome such issue, we propose an edge-based lightweight Kalman filter network (EKFNet) that does not require manual prior knowledge estimation. Approach. Specifically, we construct a multi-scale feature fusion module to capture multi-scale feature information and implicitly compute the prior knowledge. Meanwhile, we design an adaptive gain estimation module that incorporates long short-term memory and sequential channel attention module to dynamically predict the Kalman gain. Furthermore, we present an optimization strategy utilizing operator fusion and constant folding to reduce the model's computational overhead and memory footprint. Main results . Experimental results show that the EKFNet reduces the sum of the square of the distances by at least 12% and improves the cosine similarity by at least 2.2% over the state-of-the-art methods. Besides, the model optimization shortens the inference time by approximately 3.3×. The code of our EKFNet is available athttps://github.com/cathnat/EKFNet. Significance. By integrating Kalman filter with deep learning, the approach addresses the parameter-setting challenges in traditional algorithms while reducing computational overhead and memory consumption, which exhibits a good tradeoff between algorithm performance and computing power., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Human carbonic anhydrase (hCA) plays a vital role in the development and progression of tumors in hypoxic conditions. Herein we report the hCA-II and hCA-IX activities of natural products isolated from Aloe vera (L.) Burm.f., to know their potential in tumors. These isolated compounds (1-10) displayed varying degrees of inhibition against hCA-II and hCA-IX. All the compounds showed potent activity against hCA-IX with IC 50 values in the range of 2.9-29.1 μM. While for hCA-II, compounds 1, 2, 5-10 exhibited IC 50 in the range of 4.7-23.4 μM. The most effective hCA IX and II inhibitors, 2 and 5, were chosen for in vitro mechanism studies, revealing that they are competitive inhibitors. Furthermore, when tested for their cytotoxic effect on BJ (normal) cell line, all the compounds showed no cytotoxic behavior, while on Prostate cancer cells (PC-3), compounds 1, 3, 5, 7, and 9 exhibited significant antiproliferative activity. Molecular docking was also conducted within the hCA IX and hCA-II active sites to observe their binding capability. Compounds 1, 5, 7, and 9 were active against both isozymes of hCA and in the PC-3 cell line, therefore these are the best choices for further in vivo studies., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Thirteen novel hydrazone-Schiff bases (3-15) of fexofenadine were succesfully synthesized, structurally deduced and finally assessed their capability to inhibit urease enzyme (in vitro). In the series, six compounds 12 (IC 50 =10.19±0.16 μM), 11 (IC 50 =15.05±1.11 μM), 10 (IC 50 =17.01±1.23 μM), 9 (IC 50 =17.22±0.81 μM), 13 (IC 50 =19.31±0.18 μM), and 14 (IC 50 =19.62±0.21 μM) displayed strong inhibitory action better than the standard thiourea (IC 50 =21.14±0.24 μM), while the remaining compounds displayed significant to less inhibition. LUMO and HOMO showed the transferring of charges from molecules to biological transfer and MEP map showed the chemically reactive zone appropriate for drug action are calculated using DFT. AIM charges, non-bonding orbitals, and ELF are also computed. The urease protein binding analysis benefited from the docking studies., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Intraventricular hemorrhage (IVH) is a severe condition with poor outcomes and high mortality. IRRAflow® (IRRAS AB) is a new technology introduced to accelerate IVH clearance by minimally invasive wash-out. The IRRAflow® system performs active and controlled intracranial irrigation and aspiration with physiological saline, while simultaneously monitoring and maintaining a stable intracranial pressure (ICP). We addressed important aspects of the device implementation and intracranial lavage., Method: To allow versatile investigation of multiple device parameters, we designed an ex vivo lab setup. We evaluated 1) compatibility between the IRRAflow® catheter and the Silverline f10 bolt (Spiegelberg), 2) the physiological and hydrodynamic effects of varying the IRRAflow® settings, 3) the accuracy of the IRRAflow® injection volumes, and 4) the reliability of the internal ICP monitor of the IRRAflow®., Results: The IRRAflow® catheter was not compatible with Silverline bolt fixation, which was associated with leakage and obstruction. Design space exploration of IRRAflow® settings revealed that appropriate settings included irrigation rate 20 ml/h with a drainage bag height at 0 cm, irrigation rate 90 ml/h with a drainage bag height at 19 cm and irrigation rate 180 ml/h with a drainage bag height at 29 cm. We found the injection volume performed by the IRRAflow® to be stable and reliable, while the internal ICP monitor was compromised in several ways. We observed a significant mean drift difference of 3.16 mmHg (variance 0.4, p = 0.05) over a 24-hour test period with a mean 24-hour drift of 3.66 mmHg (variance 0.28) in the pressures measured by the IRRAflow® compared to 0.5 mmHg (variance 1.12) in the Raumedic measured pressures., Conclusion: Bolting of the IRRAflow® catheter using the Medtronic Silverline® bolt is not recommendable. Increased irrigation rates are recommendable followed by a decrease in drainage bag level. ICP measurement using the IRRAflow® device was unreliable and should be accompanied by a control ICP monitor device in clinical settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Haldrup et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The anti-inflammatory and analgesic drugs currently used are associated with several adverse effects and found to be highly unsafe for long-term use. Currently, nineteen novel bis-Schiff base derivatives (1-19) of flurbiprofen have been designed, prepared and assessed for in-vivo analgesic, anti-inflammatory and in vivo acute toxicity evaluation. The structures of the acquired compounds were deduced through modern spectroscopic techniques including HR-ESI-MS, 13 C-, and 1 H NMR. Amongst the series, compounds 7, 9, and 10 attributed potent activities with 93.89, 92.50, and 90.47% decreased edema, respectively compared to flurbiprofen (90.01%), however, compounds 11 and 15 exhibited significant activity of 90.00% decrease. Out of them, fourteen compounds (1-6, 8, 12-14, and 16-19) displayed good activity in the range of 68.96-86.95%. In case of an analgesic study, all the derivatives significantly (p 0.001) increased the pain threshold time particularly compound 7 had the best analgesic effect (24 ± 2.08 s) in comparison with flurbiprofen (21.66 ± 2.02 s) using hot plate test. Similarly, in the acetic acid-induced writhing test, compound 7 determined a potent inhibitory effect (60.47 %) close to flurbiprofen (59.28%). All the synthesized derivatives were found safe up to the dose of 30 mg/kg, in acute toxicity study. On a molecular scale, the synthesized compounds were modeled through a ligand-based pharmacophore study and molecular docking to have insight into the different possible interactions leading to high inhibition levels against the COX-2 enzyme., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Boswellic acids have been recognized as anti-inflammatory and immunomodulatory agents with potentials to control autoimmune and inflammatory diseases. However, their effects on T cell proliferation and activation are not fully elucidated. In this study, we investigated effects of individual compounds including β-Boswellic acids (β-BA), 11-keto-β-Boswellic acid (β-KBA), 3-O-acetyl β-Boswellic acids (β-ABA), and 3-O-acetyl-11-keto-β-Boswellic acid (β-AKBA) on human peripheral blood mononuclear cells (PBMCs) and their potential role in modulating immune responses. We showed that β-BA, KBA, and AKBA at a 0.025 µM concentration significantly reduced T cell proliferation without inducing cytotoxicity, however, ABA showed cytotoxic effects at this concentration. β-BA and KBA showed significantly reduced T cell proliferation at 0.05 µM concentration without cytotoxic effects. Interestingly, we found that AKBA at 0.025 µM concentration significantly reduced CD25 expression on both CD4 + and CD8 + T cells without cytotoxic effects. Additionally, β-BA reduced CD25 expression on both CD4 + and CD8 + T cells at 0.05 µM concentration with no cytotoxicity. In this study, we determined the optimum concentration of each of these compounds that have the potential to reduce T cell activation without cytotoxic effects. Our findings show that both β-BA and AKBA have the ability to inhibit T cell proliferation and activation without inducing cytotoxicity. Further investigations are required to fully understand the mechanisms underlying these effects and the potential therapeutic benefits of these compounds in different autoimmune and inflammatory settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cancer is a debilitating and deadly disease caused by the uncontrolled growth of aberrant cell populations. This disease cannot always be controlled with traditional therapies and medicines. Different medicines are being used for this purpose, however these medicines have their side effects and are harmful to healthy cells. A better way to cure cancer disease is by limiting the agglomeration of cancer cells, minimizing their growth and their population by destroying these harmful cells. This could be achieved by controlling the function of mitochondria and DNA in cancer cells with the use of biocompatible materials with tuneable physical properties. Accordingly, research is ongoing as to the use of nanomaterials and nanotechnology in medicine. Zinc oxide semiconductor nanoparticles have displayed good anticancer behaviour. They have unique properties such as biocompatibility, good stability, and are environmentally friendly. Owing to these characteristics, they are focused on biological applications such as drug delivery and cancer therapy. In the present research work, zinc oxide, titanium dioxide nanoparticles and titanium oxide-zinc oxide nanocomposites were successfully trailed for anti-cancer activity. Pure zinc oxide nanoparticles (ZnO NPs), titanium dioxide nanoparticles (TiO 2 NPs) and their nanocomposites (TiO 2 +ZnO NPs) were prepared by the co-precipitation technique. The structural properties were investigated by X-ray diffraction, which confirmed the Wurtzite structure of pure ZnO NPs. The morphology of the NPs was checked by scanning electron microscopy. For incident light having a higher energy band gap of nanomaterials, the electrons are excited to the conduction band and these electrons generate reactive oxygen species (ROS). The efficacy of these nanomaterials was checked by exposing the NPs to the human liver cancer cell HepG2. The MTT assay describes anticancer activity via cell viability. The cell viability of composites was observed to be greater than pure ZnO NPs. Their results showed that the structure of ZnO NPs remains the same with composites of TiO 2 NPs, but the band gap of the composite was intermediate for individual samples. It also showed that the anticancer activity of composites was also less than pure ZnO NPs which is due to the reduction of ROS generation. This is observed that nanocomposites of ZnO and TiO 2 could be effective in the development of a treatment of human liver cancer cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Central Asian Economies (CAEs) have diverse exchange rate policies. They have recorded higher volatility in the foreign exchange market since inception. High volatility of the transition era has drifted these economies towards partial dollarization. Monetary authorities in CAEs, (already have a challenge of maintaining monetary policy autonomy) have a gigantic task of price stability and stopping the spread of dollarization. This study is directed towards assessing the drivers and the determinants of foreign exchange market pressure in CAEs. The results, based on panel data analysis and the System GMM model, have provided useful insights about the exchange market pressure determinants particularly USD, Euro, Ruble, and Renminbi. The results show that China and Russia exchange market pressure has a negative effect on the exchange market pressure of CAEs. While the dollar index shows a positive impact on the exchange market pressure of CAEs. Overall, the findings imply that China and Russia currency appreciation results in a trade deficit across CAEs. The policy implication suggests that the floating exchange rate regime (inflation targeting regime) is not in favor of CAEs, and they must use managed-float to reduce their trade deficits., Competing Interests: Competing InterestsThe authors declare that they have no competing interests" in this section., (© The Author(s) 2023.)

Endophytic bacteria boost host plant defense and growth by producing vital compounds. In the current study, a bacterial strain was isolated from the Boswellia sacra plant and identified as Bacillus subtilis strain EP1 (accession number: MT256301) through 16S RNA gene sequencing. From the identified bacteria, four compounds- 1 (4-(4-cinnamoyloxy)phenyl)butanoic acid), 2 (cyclo-(L-Pro-D-Tyr)), 3 (cyclo-(L-Val-L-Phe)), and 4 (cyclo-(L-Pro-L-Val))-were isolated and characterized by 1D and 2D NMR and mass spectroscopy. Moreover, antibacterial activity and beta-lactam-producing gene inhibition (δ-(l-α-aminoadipyl)-l-cysteinyl-d-valine synthetase (ACVS) and aminoadipate aminotransferase (AADAT)) assays were performed. Significant antibacterial activity was observed against the human pathogenic bacterial strains ( E. coli ) by compound 4 with a 13 ± 0.7 mm zone of inhibition (ZOI), followed by compound 1 having an 11 ± 0.7 mm ZOI. In contrast, the least antibacterial activity among the tested samples was offered by compound 2 with a 10 ± 0.9 mm ZOI compared to the standard (26 ± 1.2 mm). Similarly, the molecular analysis of beta-lactam inhibition determined that compounds 3 and 4 inhibited the two genes (2- to 4-fold) in the beta-lactam biosynthesis (ACVS and AADAT) pathway. From these results, it can be concluded that future research on these compounds could lead to the inhibition of antibiotic-resistant pathogenic bacterial strains.

Copper (Cu 2+ ) toxicity can inhibit plant growth and development. It has been shown that silicon (Si) can relieve Cu 2+ stress. However, it is unclear how Si-nanoparticles (SiNPs) relieve Cu 2+ stress in wheat seedlings. Therefore, the current study was conducted by setting up four treatments: CK, SiNP: (2.5 mM), Cu 2+ : (500 µM), and SiNP+Cu 2+ : (2.5 mM SiNP+500 µM Cu 2+ ) to explore whether SiNPs can alleviate Cu 2+ toxicity in wheat seedlings. The results showed that Cu 2+ stress hampered root and shoot growth and accumulated high Cu 2+ concentrations in roots (45.35 mg/kg) and shoots (25.70 mg/kg) of wheat as compared to control treatment. Moreover, Cu 2+ treatment inhibited photosynthetic traits and chlorophyll contents as well as disturbed the antioxidant defense system by accumulating malondialdehyde (MDA) and hydrogen peroxidase (H 2 O 2 ) contents. However, SiNPs treatment increased root length and shoot height by 15.1% and 22%, respectively, under Cu 2+ toxicity. Moreover, SiNPs application decreased MDA and H 2 O 2 contents by 31.25% and 19.25%, respectively. SiNPs increased non-enzymatic compounds such as ascorbic acid-glutathione (AsA-GSH) and enhanced superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbic peroxidase (APX) activities by 77.5%, 141.7%, 68%, and 80%, respectively. Furthermore, SiNPs decreased Cu 2+ concentrations in shoots by 26.2%, as compared to Cu 2+ treatment alone. The results concluded that SiNPs could alleviate Cu 2+ stress in wheat seedlings. The present investigation may help to increase wheat production in Cu 2+ contaminated soils., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Riaz, Zhao, Kamran, Ur Rehman, Mora-Poblete, Maldonado, Hamzah Saleem, Parveen, Ahmed Al-Ghamdi, Al-Hemaid, Ali and Elshikh.)

Encouraged by the potent anti-depression activities of incensole (1) and incensole acetate (2) isolated from the resin of Boswellia papyrifera in our previous work, different derivatives of 1 and 2 were synthesized in the present study. The reaction of 1 with m-CPBA afforded the mono-epoxide derivative 3a, while the same reaction with 2 led to three different epoxide derivatives 3a, 3b, and 3c. Oxidation of 1 with PCC to get compound 3b, however along with the target 3b, the reaction gave three interesting side products (3c-3e). Oxime (3b-1) resulted from the reaction of 3b with hydroxylamine hydrochloride in pyridine, while epoxidation of 2 generate three epoxide products (4a-4c). The structures of all products were unambiguously confirmed using NMR and Mass spectrometry. Compounds 3a-e and 4a-c (0.1-3 mg/kg, i.p.) demonstrated promising anti-depression activities in classical mouse models of depression of FST and TST. The results showed that compounds 3a-e and 4a-c (0.1-3 mg/kg, i.p.) caused dose dependent reduction in immobility time compared to the vehicle control, with 3c-3e and 4b-4c demonstrating higher potency and efficacy. The findings of the open field test excluded the motor effects of these compounds, thus further confirming their anti-depression activity. Preliminary investigation into their mechanism of action using GABA antagonist, PTZ and molecular docking has predicted that compounds 3e and 4c bind at the GABA binding site of GABA A receptor to produce GABAergic effects. Furthermore, the promising anti-depression potency of compounds 1 and 2 and their derivatives make them lead compounds for drug discovery., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Rationale: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and cognitive behaviors. Histamine H3 receptor (H3R) antagonists are considered as therapeutic factors for treating cognitive impairments., Objectives: The aim of the present study was to evaluate the effects of the H3R antagonist, ciproxifan (CPX), on cognition impairment especially, spatial learning memory, and synaptic plasticity in the CA1 region of the hippocampus in autistic rats., Methods: Pregnant rats were injected with either valproic acid (VPA) (600 mg/kg, i.p.) or saline on an embryonic day 12.5 (E12.5). The effects of the H3R antagonist, ciproxifan (CPX) (1, 3 mg/kg, i.p.), were investigated on learning and memory in VPA-exposed rat pups and saline-exposed rat pups using Morris water maze (MWM) and social interaction tasks. The H2R antagonist, famotidine (FAM) (10, 20, 40 mg/kg, i.p.), was used to determine whether brain histaminergic neurotransmission exerted its procognitive effects through the H2R. In addition, synaptic reinforcement was evaluated by in vivo field potential recording., Results: The results showed that VPA-exposed rat pups had significantly lower sociability and social memory performance compared to the saline rats. VPA-exposed rat pups exhibited learning and memory impairments in the MWM task. In addition, VPA caused suppression of long-term potentiation (LTP) in the CA1 area of the hippocampus. Our results demonstrated that CPX 3 mg/kg improved VPA-induced cognitive impairments and FAM 20 mg/kg attenuated cognitive behaviors as well as electrophysiological properties., Conclusions: CPX 3 mg/kg improved VPA-induced impairments of LTP as well as learning and memory deficits through H2R., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The recent study investigated the in vitro anti-diabetic impact of the crude extract (MeOH) and subfractions ethyl acetate (EtOAc); chloroform; n-butanol; n-hexane; and aqueous fraction of S. edelbergii and processed the active EtOAc fraction for the identification of chemical constituents for the first time via ESI-LC-MS analysis through positive ionization mode (PIM) and negative ionization mode (NIM); the identified compounds were further validated through computational analysis via standard approaches. The crude extract and subfractions presented appreciable activity against the α-glucosidase inhibitory assay. However, the EtOAc fraction with IC 50 = 0.14 ± 0.06 µg/mL revealed the maximum potential among the fractions used, followed by the MeOH and n-hexane extract with IC 50 = 1.47 ± 0.14 and 2.18 ± 0.30 µg/mL, respectively. Moreover, the acarbose showed an IC 50 = 377.26 ± 1.20 µg/ mL whereas the least inhibition was observed for the chloroform fraction, with an IC 50 = 23.97 ± 0.14 µg/mL. Due to the significance of the EtOAc fraction, when profiled for its chemical constituents, it presented 16 compounds among which the flavonoid class was dominant, and offered eight compounds, of which six were identified in NIM, and two compounds in PIM. Moreover, five terpenoids were identified-three and two in NIM and PIM, respectively-as well as two alkaloids, both of which were detected in PIM. The EtOAc fraction also contained one phenol that was noticed in PIM. The detected flavonoids, terpenoids, alkaloids, and phenols are well-known for their diverse biomedical applications. The potent EtOAc fraction was submitted to computational analysis for further validation of α-glucosidase significance to profile the responsible compounds. The pharmacokinetic estimations and protein-ligand molecular docking results with the support of molecular dynamic simulation trajectories at 100 ns suggested that two bioactive compounds-dihydrocatalpol and leucosceptoside A-from the EtOAc fraction presented excellent drug-like properties and stable conformations; hence, these bioactive compounds could be potential inhibitors of alpha-glucosidase enzyme based on intermolecular interactions with significant residues, docking score, and binding free energy estimation. The stated findings reflect that S. edelbergii is a rich source of bioactive compounds offering potential cures for diabetes mellitus; in particular, dihydrocatalpol and leucosceptoside A could be excellent therapeutic options for the progress of novel drugs to overcome diabetes mellitus.

Polyfumarate has been considered as injectable and biodegradable bone cement. However, its mechanical and degradation properties are particularly important. Therefore, the current study aimed to develop the properties by compositing poly (butyl fumarate)-based networks with hydroxyapatite nano-powders. In this regard, the poly (butyl fumarate) (PBF) matrix composite was compared with different components by evaluating their composition, mechanical properties, hydrophilicity, and biodegradability. Furthermore, their bioactivity in the phosphate-buffered saline (PBS) and, via applying mouse embryo osteoblast precursor cells (MC3T3-E1), their cell interaction, including adhesion, proliferation, and in vitro cytotoxicity assay, were assessed. The addition of hydroxyapatite improved the mechanical strength and modulus of PBF matrix composite. The composite reinforced with 3 wt% hydroxyapatite showed a higher lap-shear strength (1.68 MPa) and bonding strength (4.30 MPa), a maximum compression strength at fracture (95.18 MPa), modulus (925.29 MPa), and compression strength at yield (31.43 MPa), respectively. Also, hydrophilicity and in vitro degradation of the composite were enhanced in the presence of hydroxyapatite. In this condition, after a period of immersion (52 weeks) in PBS, the weight loss rate, and degradation rate of the composite increased. The composite proliferation, adhesion, and toxicity of MC3T3-E1 cells improved in comparison to the PBF matrix composite. Accordingly, controllable strength and degradation of the composite, along with its proven biocompatibility, make the composite a candidate for the treatment of comminuted fractures., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Carbonic anhydrase-II (CA-II) is strongly related with gastric, glaucoma, tumors, malignant brain, renal and pancreatic carcinomas and is mainly involved in the regulation of the bicarbonate concentration in the eyes. With an aim to develop novel heterocyclic hybrids as potent enzyme inhibitors, we synthesized a series of twelve novel 3-phenyl-β-alanine 1,3,4-oxadiazole hybrids ( 4a - l ), characterized by 1 H- and 13 C-NMR with the support of HRESIMS, and evaluated for their inhibitory activity against CA-II. The CA-II inhibition results clearly indicated that the 3-phenyl-β-alanine 1,3,4-oxadiazole derivatives 4a - l exhibited selective inhibition against CA-II. All the compounds (except 4d ) exhibited good to moderate CA-II inhibitory activities with IC 50 value in range of 12.1 to 53.6 µM. Among all the compounds, 4a (12.1 ± 0.86 µM), 4c (13.8 ± 0.64 µM), 4b (19.1 ± 0.88 µM) and 4h (20.7 ± 1.13 µM) are the most active hybrids against carbonic CA-II. Moreover, molecular docking was performed to understand the putative binding mode of the active compounds. The docking results indicates that these compounds block the biological activity of CA-II by nicely fitting at the entrance of the active site of CA-II. These compounds specifically mediating hydrogen bonding with Thr199, Thr200, Gln92 of CA-II.

The current study aimed to explore the crude oils obtained from the n-hexane fraction of Scutellaria edelbergii and further analyzed, for the first time, for their chemical composition, in vitro antibacterial, antifungal, antioxidant, antidiabetic, and in vivo anti-inflammatory, and analgesic activities. For the phytochemical composition, the oils proceeded to gas chromatography-mass spectrometry (GC-MS) analysis and from the resultant chromatogram, 42 bioactive constituents were identified. Among them, the major components were linoleic acid ethyl ester (19.67%) followed by ethyl oleate (18.45%), linolenic acid methyl ester (11.67%), and palmitic acid ethyl ester (11.01%). Tetrazolium 96-well plate MTT assay and agar-well diffusion methods were used to evaluate the isolated oil for its minimum inhibitory concentrations (MIC), minimum bactericidal concentration (MBC), half-maximal inhibitory concentrations (IC 50 ), and zone of inhibitions that could determine the potential antimicrobial efficacy's. Substantial antibacterial activities were observed against the clinical isolates comprising of three Gram-negative bacteria, viz., Escherichia coli , Klebsiella pneumoniae , and Pseudomonas aeruginosa , and one Gram-positive bacterial strain, Enterococcus faecalis . The oils were also effective against Candida albicans and Fusarium oxysporum when evaluated for their antifungal potential. Moreover, significant antioxidant potential with IC 50 values of 136.4 and 161.5 µg/mL for extracted oil was evaluated through DPPH (1,1-Diphenyl-2-picryl-hydrazyl) and ABTS assays compared with standard ascorbic acid where the IC50 values were 44.49 and 67.78 µg/mL, respectively, against the tested free radicals. The oils was also potent, inhibiting the α-glucosidase (IC50 5.45 ± 0.42 µg/mL) enzyme compared to the standard. Anti-glucosidase potential was visualized through molecular docking simulations where ten compounds of the oil were found to be the leading inhibitors of the selected enzyme based on interactions, binding energy, and binding affinity. The oil was found to be an effective anti-inflammatory (61%) agent compared with diclofenac sodium (70.92%) via the carrageenan-induced assay. An appreciable (48.28%) analgesic activity in correlation with the standard aspirin was observed through the acetic acid-induced writhing bioassay. The oil from the n-hexane fraction of S. edelbergii contained valuable bioactive constituents that can act as in vitro biological and in vivo pharmacological agents. However, further studies are needed to uncover individual responsible compounds of the observed biological potentials which would be helpful in devising novel drugs.

In continuation of phytochemical investigations of the methanolic extract of Dictyopteris hoytii, we have obtained twelve compounds ( 1 - 12 ) through column chromatography. Herein, three compounds, namely, dimethyl 2-bromoterepthalate ( 3 ), dimethyl 2,6-dibromoterepthalate ( 4 ), and ( E )-3-(4-(dimethoxymethyl)phenyl) acrylic acid ( 5 ) are isolated for the first time as a natural product, while the rest of the compounds ( 1 , 2 , 6 - 12 ) are known and isolated for the first time from this source. The structures of the isolated compounds were elucidated by advanced spectroscopic 1D and 2D NMR techniques including 1 H, 13 C, DEPT, HSQC, HMBC, COSY, NEOSY, and HR-MS and comparison with the reported literature. Furthermore, eight compounds ( 13 - 20 ) previously isolated by our group from the same source along with the currently isolated compounds ( 1 - 12 ) were screened against the CA-II enzyme. All compounds, except 6 , 8 , 14 , and 17 , were evaluated for in vitro bovine carbonic anhydrase-II (CA-II) inhibitory activity. Eventually, eleven compounds ( 1 , 4 , 5 , 7 , 9 , 10 , 12 , 13 , 15 , 18 , and 19 ) exhibited significant inhibitory activity against CA-II with IC 50 values ranging from 13.4 to 71.6 μM. Additionally, the active molecules were subjected to molecular docking studies to predict the binding behavior of those compounds. It was observed that the compounds exhibit the inhibitory potential by specifically interacting with the ZN ion present in the active site of CA-II. In addition to ZN ion, two residues (His94 and Thr199) play an important role in binding with the compounds that possess a carboxylate group in their structure.

Objective: The present study was aimed to assess knowledge regarding disease, adherence to medication and blood pressure control among hypertensive patients., Methods: A cross-sectional study involving 384 hypertensive patients attending a tertiary care, public sector hospital in Islamabad, Pakistan, was conducted. Data was collected by using Urdu versions of pre-validated hypertension knowledge questionnaire and Medication Adherence Scale by Morisky. Each patient's blood pressure was measured through a calibrated mercury sphygmomanometer. Data was analyzed statistically by using SPSS software version 21.0. Chi-square test was performed to determine association level among study variables. Mann-Whitney and Kruskal-Wallis tests were performed to assess for statistically significant differences of demographic variables with systolic BP and diastolic BP. Multiple regression was used to predict the impact of two or more independent variables on dependent variable. P value of <.05 was considered to be significant., Results: Mean (SD) systolic and diastolic blood pressures of 384 patients were 140.39 ± 15.485 and 88.74 ± 10.683 in mmHg respectively. The mean knowledge score was (13.26 ± 5.16 out of 22) and median score was 13. 103 (26.8%) of the patients had poor knowledge, whereas, 191 (49.7%) had moderate knowledge regarding hypertension with most of them at bottom line in the scale of moderate knowledge. The mean medication adherence score was (4.66 ± 2.743 out of 8), while 204 (53.1%) were categorized as poor adherent., Conclusion: The current study concluded that knowledge regarding hypertension, adherence to treatment and blood pressure control among hypertensive patients was found poor.

Background: Salmonella enterica serotype Typhi (S Typhi) is a major public health problem in low-income and middle-income countries. We aimed to investigate the effectiveness and impact of the typhoid conjugate vaccine Typbar-TCV against S Typhi among children in an outbreak setting of extensively drug-resistant (XDR) S Typhi in Pakistan., Methods: This cohort study was done from Feb 21, 2018, to Dec 31, 2019. A census survey of all households located in the Qasimabad and Latifabad subdistricts of Hyderabad, Pakistan, was done at baseline, and 174 005 households were registered in the census. The Typbar-TCV immunisation campaign was initiated at temporary vaccination centres and 207 000 children aged 6 months to 10 years were vaccinated from Feb 21, 2018, to Dec 31, 2018. Social mobilisers informed parents about the vaccination process. Vaccination records were maintained electronically and linked with the household census surveys. Active surveillance for suspected and blood-culture-confirmed S Typhi was established in hospitals, clinics, and laboratories to assess the following outcomes: cases of suspected typhoid fever, culture-confirmed S Typhi, and antimicrobial resistance. An age-stratified cohort of 1100 vaccinated children was randomly selected from the vaccination registry, tested for Vi-IgG antibodies (data not reported), and followed up fortnightly (via telephone calls or household visits) until Dec 31, 2019, for ascertainment of outcomes during the study period. 20 847 vaccinated and unvaccinated children were randomly selected from the census registry as a quality control cohort and followed up from Oct 1 to Dec 31, 2019, for ascertainment of outcomes. Vaccine effectiveness against suspected, culture-confirmed, and XDR S Typhi was calculated., Findings: 23 407 children from the census registry and surveillance system were included in the vaccine effectiveness analysis. 13 436 (57·4%) children were vaccinated, 12 214 (52·2%) were male, and 10 168 (43·4%) were aged 6-59 months. 5378 (23·0%) of 23 407 children had suspected S Typhi, among whom 775 (14·4%) had culture-confirmed S Typhi and 361 (68·6%) of 526 had XDR S Typhi. Vaccine effectiveness was 55% (95% CI 52-57) against suspected S Typhi (regardless of culture confirmation), 95% (93-96) against culture-confirmed S Typhi, and 97% (95-98) against XDR S Typhi., Interpretation: Typbar-TCV is effective in protecting children against S Typhi infection in an outbreak setting, and was able, with moderate deployment, to curtail a major XDR S Typhi outbreak in a densely populated setting. The vaccine shows efficacy against S Typhi irrespective of antimicrobial resistance., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests NB-Z received investigator-initiated research grants unrelated to this work from Merck, the Serum Institute of India, and PATH Seattle. NB-Z served on the data safety monitoring board for a study at the University of Oxford, Oxford, UK (Pancreatic Enzymes and Bile Acids: A Non-Antibiotic Approach to Intestinal Dysbiosis in Acutely Ill Severely Malnourished Children. A Placebo Controlled Double Blind Randomised Controlled Trial in Kenya and Malawi), and received a nominal fee as a scientific advisory committee member for the COVID-19 Vaccines International Pregnancy Exposure Registry. NB-Z reports two discussions with Bharat Biotech International relating to the design and evaluation of a specific product. This advice was provided pro bono, and under no contractual arrangement other than non-disclosure about the product in question. These discussions are unrelated to the company's typhoid conjugate vaccine that was evaluated in this Article. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

We aimed to determine the frequency of depression, anxiety and insomnia; identify associated factors; and compare these outcomes amongst a privileged and underprivileged class of Pakistan. A cross-sectional online and face to face survey was conducted in Karachi from April 2020 to May 2020. Validated depression (World Health Organization self-reporting questionnaire), anxiety (general anxiety and depression scale) and insomnia (insomnia severity index) scales were used. Out of 447 participants, the majority were less than 30 years (63.8%) and females (57.7%); 20.8% study participants belonged to poor or very poor socioeconomic status; 17% respondents were from lower middle status and 38% belonged to the higher middle or rich class. Depression, anxiety and insomnia were identified in 30%, 30.63% and 8.5% of participants, respectively. The prevalence of depression, anxiety and insomnia among privileged people was 37.8%, 16.6% and 11.3% respectively whereas among underprivileged were 17.8%, 16.6% and 4.1% respectively. There were significant differences in frequencies of depression (p<0.001), anxiety (p<0.001) and insomnia (p=0.009) among the privileged and underprivileged classes. We found a high prevalence of depression, anxiety and insomnia among both the privileged and underprivileged Pakistani population and a policy needs to be devised to ensure the mental health of Pakistani population.

In the current study, in vitro antimicrobial and antioxidant activities and in vivo anti-inflammatory and analgesic activities of Scutellaria edelbergii Rech. f. (crude extract and subfractions, i.e., n-hexane, ethyl acetate (EtOAc), chloroform, n-butanol (n-BuOH) and aqueous) were explored. Initially, extraction and fractionation of the selected medicinal plant were carried out, followed by phytochemical qualitative tests, which were mostly positive for all the extracts. EtOAc fraction possessed a significant amount of phenolic (79.2 ± 0.30 mg GAE/g) and flavonoid (84.0 ± 0.39 mg QE/g) content. The EtOAc fraction of S. edelbergii exhibited appreciable antibacterial activity against Gram-negative ( Escherichia coli and Klebsiella pneumoniae ) strains and significant zones of inhibition were observed against Gram-positive bacterial strains ( Bacillus subtilis and Staphylococcus aureus ). However, it was found inactive against Candida Albicans and Fusarium oxysporum fungal strains. The chloroform fraction was the most effective with an IC 50 value of 172 and 74 µg/mL against DPPH (1,1-Diphenyl-2-picryl-hydrazyl) and ABTS assays, in comparison with standard ascorbic acid 59 and 63 µg/mL, respectively. Moreover, the EtOAc fraction displayed significant in vivo anti-inflammatory activity (54%) using carrageenan-induced assay and significant (55%) in vivo analgesic activity using acetic acid-induced writing assay. In addition, nine known compounds, ursolic acid ( UA ), ovaul ( OV ), oleanolic acid ( OA ), β-sitosterol ( BS ), micromeric acid ( MA ), taraxasterol acetate ( TA ), 5,3',4'-trihydroxy-7-methoxy flavone ( FL-1 ), 5,7,4'-trihydroxy-6,3'-dimiethoxyflavone ( FL-2 ) and 7-methoxy catechin ( FL-3 ), were isolated from methanolic extract of S. edelbergii . These constituents have never been obtained from this source. The structures of all the isolated constituents were elucidated by spectroscopic means. In conclusion, the EtOAc fraction and all other fractions of S. edelbergii , in general, displayed a significant role as antibacterial, free radical scavenger, anti-inflammatory and analgesic agents which may be due to the presence of these constituents and other flavonoids.

The aim of this study was to evaluate a bioactive multilayer wound dressing, based on chitosan and alginate. To enhance healing potential, Dracaena Cinnabari and Aloe Vera were loaded as separate layers into the scaffold. The bare and bioactive multilayered scaffolds were fabricated by an iterative layering freeze-drying technique. Following of topographical, chemical, and physical assessment, the performance of the scaffolds was evaluated in vitro and in vivo. The results revealed adequate attachment, and proliferation of human foreskin fibroblasts, indicating excellent biocompatibility of the bioactive scaffold. In vivo, the performance of the multi-layered scaffold loaded with the bioactive materials was comparable with Comfeel plus®. The wounds treated with the bioactive scaffold exhibited superior hypergranulation, fibroblast maturation, epithelization, and collagen deposition, with minimal inflammation, and crust formation. It is concluded that the synergism of extracellular matrix-mimicking multi-layered scaffolding with Aloe Vera and Dracaena Cinnabari could be considered as a supportive wound dressing., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In the study, two novel compounds along with two new compounds were isolated from Grewia optiva . The novel compounds have never been reported in any plant source, whereas the new compounds are reported for the first time from the studied plant. The four compounds were characterized as: 5,5,7,7,11,13-hexamethyl-2-(5-methylhexyl)icosahydro-1H-cyclopenta[a]chrysen-9-ol ( IX ), docosanoic acid ( X ), methanetriol mano formate ( XI ) and 2,2'-(1,4-phenylene)bis(3-methylbutanoic acid (XII) . The anticholinesterase, antidiabetic, and antioxidant potentials of these compounds were determined using standard protocols. All the isolated compounds exhibited a moderate-to-good degree of activity against acetylcholinesterases (AChE) and butyrylcholinesterase (BChE). However, compound XII was particularly effective with IC 50 of 55 μg/mL (against AChE) and 60 μg/mL (against BChE), and this inhibitory activity is supported by in silico docking studies. The same compound was also effective against DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid) radicals with IC 50 values of 60 and 62 μg/mL, respectively. The compound also significantly inhibited the activities of α-amylase and α-glucosidase in vitro. The IC 50 values for inhibition of the two enzymes were recorded as 90 and 92 μg/mL, respectively. The in vitro potentials of compound XII to treat Alzheimer's disease (in terms of AchE and BChE inhibition), diabetes (in terms of α-amylase and α-glucosidase inhibition), and oxidative stress (in terms of free radical scavenging) suggest further in vivo investigations of the compound for assessing its efficacy, safety profile, and other parameters to proclaim the compound as a potential drug candidate.

A series of new 11-keto-β-boswellic acid were partially-synthesized by modifying the hydroxyl and carboxylic acid functional groups of ring A. The structures of the new analogs were confirmed by detailed spectral data analysis. Compounds 4 , 5 and 9 exhibited potent anti-cancer results against two human tumor cancer cell lines having IC 50 value of MCF-7 (breast) and LNCaP (prostate): 123.6, 9.6 and 88.94 μM and 9.6, 44.12 and 12.03 μM, respectively. Additionally, a maximum nuclear fragmentation was observed for 4 (78.44%) in AKBA treated cells after 24 hr followed by 5 and 9 with (74.25 and 66.9% respectively). This study suggests that the presence of hydrazone functionality ( 4 and 9 ) has effectively improved the potency of AKBA. Interestingly, compound 5 with a lost carboxylic acid group of ring A showed comparable potent activity. Highly selective AKBA requires further modification to improve its bioavailability and solubility inside the cancer cells.

Otostegia fruticosa is traditionally used to treat tonsillitis, stomach ache, asthma, arthritis, and febrile illness in different parts of Ethiopia and other countries. In this experiment 70% ethanolic crude extract and fractions of the leaf of Otostegia fruticosa (Forssk.) Schweinf. ex Penzig were evaluated for their in-vivo anti-inflammatory and analgesic activities and in-vitro hyaluronidase inhibition properties at different concentrations. Tail immersion, acetic acid induced writhing and carrageenan-induced paw edema model were used to assess the in-vivo analgesic and anti-inflammatory activities, respectively. Swiss albino mice of either sex were randomly divided into five groups of six mice per group and for evaluation of the fractions randomly divided into six groups of six mice per group. The test groups were treated with hydroalcoholic extract of Otostegia fruticosa (O. fruticosa) at doses of 100, 200, and 400 mg/kg. The positive control groups received either pethidine 5 mg/kg or aspirin at 100 mg/kg or 150 mg/kg. The negative control groups were orally given sunflower oil. All the fractions were administered at the dose of 400 mg/kg. In all models, the higher dose (400 mg/kg) of the crude extract and chloroform fraction showed a significant central and peripheral analgesic and anti-inflammatory activities with comparable effects to standards used. The hyaluronidase inhibition assay result showed that the test samples displayed concentration-dependent inhibitory activities. These findings indicate that 70% ethanol extract and organic solvent fractions of O. fruticosa leaves have potential analgesic, anti-inflammatory, and enzyme inhibitory activities.

Introduction: Physical, chemical, thermal injuries along with infectious diseases lead to acute pain with associated inflammation, being the primary cause of hospital visits. Moreover, neuropathic pain associated with diabetes is a serious chronic disease leading to high morbidity and poor quality of life., Objective: Earlier multiple sulphonamides have been reported to have an antinociceptive and antiallodynic profile. 4-Fluoro-N-(4-sulfamoylbenzyl) Benzene Sulfonamide (4-FBS), a synthetic sulfonamide with reported carbonic anhydrase inhibitory activity, was investigated for its potential effects in mice model of acute and diabetic neuropathic pain., Methods and Results: 4-FBS was given orally (p.o.) one hour before the test and then mice were screened for antinociceptive activity by using the tail immersion test, which showed significant antinociceptive effect at both 20 and 40 mg/kg doses. To explore the possible mechanisms, thermal analgesia of 4-FBS was reversed by the 5HT 3 antagonist ondansetron 1mg/kg intraperitoneally (i.p.) and by the µ receptor antagonist naloxone (1 mg/kg i.p.), implying possible involvement of serotonergic and opioidergic pathways in the analgesic effect of 4-FBS. Diabetes was induced in mice by a single dose of streptozotocin (STZ) 200 mg/kg i.p. After two weeks, animals first became hyperalgesic and progressively allodynic in the fourth week, which was evaluated through behavioral parameters like thermal and mechanical tests. 4-FBS at 20 and 40 mg/kg p.o. significantly reversed diabetes-induced hyperalgesia and allodynia at 30, 60, 90, and 120 minutes., Conclusion: These findings are significant and promising while further studies are warranted to explore the exact molecular mechanism and the potential of 4-FBS in diabetic neuropathic pain., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Ur Rehman et al.)

Methylphenidate (MPH) abuse is prevalent among youth. Drug abuse results in pain perception. We sought to investigate whether Maternal separation (MS) prone to MPH addiction. The next question was whether MPH abusers with MS differ in pain perception. We investigated the impact of MS on addiction and drug reward as well as pain perception following 5 days of MPH injection in males and females rats. Initially, rats underwent MS protocol of 3 hr daily for 21 days. Conditioned place preference (CPP) test was an attempt to investigate whether MS rats experience more reward with MPH. The protocol consisted of 10 min habituation on Day 1, conditioning on Day 2-Day 6 (5 mg per kg MPH injection in drug compartment and saline in saline compartment with 4 hr gap between injections) and 10 min test on Day 7. Furthermore, using another group, differences in pain perception were investigated after 5 days of daily MPH injection with 5 mg per kg. Sensory pain sensitivity was tested on PND 39 using tail flick and hotplate in MS and control groups with and without MPH exposure. Results indicated that female rats are equally prone to addiction in CPP. On the other hand, MS males experience a higher reward in CPP. In tail flick test, female MS rats exposed to MPH show a lower sensory pain threshold with similar MPH exposure. Experiencing MPH similarly declined hotplate pain perception in MS and controls in the females. Males, on the other hand, did not show any difference in sensory pain tests. According to results one can argue MS is detrimental. MS males experience more reward with MPH, females are equally addiction prone and MS females experience more pain in tail flick. On the other hand pain threshold can decline in hotplate test for both control and MS females that received MPH., (© 2020 International Society for Developmental Neuroscience.)

Introduction: Behavioral sensitization is a phenomenon that develops from intermittent exposure to nicotine and other psychostimulants, which often leads to heightened locomotor activity and then relapse. Sulfonamides that act as carbonic anhydrase inhibitors have a documented role in enhancing dopaminergic tone and normalizing neuroplasticity by stabilizing glutamate release., Objective: The aim of the current study was to explore synthetic sulfonamides derivative 4-fluoro-N-(4-sulfamoylbenzyl) benzene-sulfonamide (4-FBS) (with documented carbonic anhydrase inhibitory activity) on acquisition and expression of nicotine-induced behavioral sensitization., Methods: In the acquisition phase, selected 5 groups of mice were exposed to saline or nicotine 0.5mg/kg intraperitoneal (i.p) for 7 consecutive days. Selected 3 groups were administered with 4-FBS 20, 40, and 60 mg/kg p.o. along with nicotine. After 3 days of the drug-free period, ie, day 11, a challenge dose of nicotine was injected to all groups except saline and locomotor activity was recorded for 30 minutes. In the expression phase, mice were exposed to saline and nicotine only 0.5 mg/kg i.p for 7 consecutive days. After 3 days of the drug-free period, ie, day 11, 4-FBS at 20, 40, and 60 mg/kg were administered to the selected groups, one hour after drug a nicotine challenge dose was administered, and locomotion was recorded. At the end of behavioral experiments, all animals were decapitated and the striatum was excised and screened for changes in adenosine levels, using HPLC-UV., Results: Taken together, our findings showed that 4-FBS in all 3 doses, in both sets of experiments significantly attenuated nicotine-induced behavioral sensitization in mice. Additionally, 4-FBS at 60mg/kg significantly lowered the adenosine level in the striatum., Conclusion: The behavioral and adenosine modulation is promising, and more receptors level studies are warranted to explore the exact mechanism of action of 4-FBS., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Ur Rehman et al.)

Materials and Methods: Aqueous-methanolic crude extracts of Flaxseed (Fs.Cr) and Flaxseed oil were tested against 6% acetic acid- (AA-) induced colitis in BALB/c mice. Microscopic damage parameters of the hematoxylin and eosin-stained and periodic acid-Schiff-alcian blue-stained sections of the colon were scored to be assessed. Possible antispasmodic mechanism was studied on isolated rabbit jejunum, while antibacterial activity was assessed in vitro for microbes implicated in IBD., Results: In AA-induced colitis, Flaxseed oil was found to be more effective in reducing mortality and colonic ulcers than Fs.Cr at 500 mg/kg dose. Fs.Cr was more efficacious in increasing mucin content as compared to oil, exhibiting slightly greater anti-inflammatory effect (50% vs 35%) and reducing depth of lesion (55% vs 42.31%, respectively). Antispasmodic activity of Fs.Cr (0.03 and 0.1 mg/ml) was mediated by phosphodiesterase inhibitors (PDEI, possibly PDE-4 subtype) with a resultant increase in cAMP levels. Flaxseed oil PDEI activity was mild (1 and 3 mg/ml). Fs.Cr (0.1 and 0.3 mg/ml) was potent in exhibiting anticholinergic activity, similar to dicyclomine, whereas Flaxseed oil showed anticholinergic effect at 1 and 3 mg/ml. Flaxseed oil (9 and 14  µ g/ml) was bactericidal against enteropathogenic E.coli (EPEC), enterotoxigenic E.coli (ETEC), and enteroaggregative E.coli (EAEC), whereas Fs.Cr exhibited bactericidal effect against EPEC at 100  µ g/ml., Conclusions: Results of this study, taken together with previous studies, suggest that Flaxseed possesses anti-inflammatory, antibacterial, and antispasmodic action through multiple pathways and thus offers promising potential to be developed for IBD., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Amber Hanif Palla et al.)

In the current investigation, a series of heterocyclic derivatives of boswellic acids were prepared along with new monomers of 3- O -acetyl-11-keto-β-boswellic acid (AKBA, 1 ) 11-keto-β-boswellic acid (KBA, 2 ) and several new bis-AKBA and KBA homodimers and AKBA-KBA heterodimers. The effects of these compounds on the proliferation of different human cancer cell lines, viz., FaDu (pharynx carcinoma), A2780 (ovarian carcinoma), HT29 (colon adenocarcinoma), and A375 (malignant melanoma), have been evaluated. Thus, KBA homodimer 21 effectively inhibited the growth of FaDu, A2780, HT29, and A375 cells with EC 50 values below 9 μM. In addition, compounds 7 , 8 , 11 , 12 , 15 , 16, and 17 also exhibited cytotoxic effects for A2780, HT29, and A375 cancer cells. In particular, the pyrazine analog 8 was highly cytotoxic for A375 cancer cells with an EC 50 value of 2.1 μM.

The study was aimed to evaluate in vitro antioxidant, α-amylase inhibitory and in vivo antidiabetic activities of Myrica salicifolia root extracts. The powdered roots of M. salicifolia were extracted with 80% methanol and then dried. The dried extract was further fractionated into chloroform, ethyl acetate, butanol and aqueous fractions. The phytochemical screening of the crude extract was performed using standard chemical identification tests. The antioxidant activity of the extracts was determined by in vitro method using 2,2-diphenyl-1-picrylhydrazyl (DPPH) as radical scavenging reagent. The in vitro α-amylase inhibitory activity was performed using the chromogenic3,5-dinitrosalicylic (DNSA) method. The antidiabetic activity of M. salicifolia root crude extract (200, 400 and 600 mg/kg) and fractions (400 mg/kg) were evaluated in normal, glucose loaded hyperglycemic and streptozotocin (STZ)-induced diabetic mice. The crude root extract of M. salicifolia showed strong DPPH radical scavenging activity (IC50 = 4.54µg/ml) which was comparable with the standard antioxidant, ascorbic acid. In α-amylase inhibitory activity, the crude extract and butanol fraction showed highest enzyme inhibition. In the antidiabetic activity, daily administration of the crude extract, aqueous and butanol fractions for fifteen days showed highest significant reduction in fasting blood glucose level (BGL) compared to diabetic control in STZ-induced diabetic mice model. The root extract and fractions of M. salicifolia exhibited significant antihyperglycemic, α-amylase inhibitory and antioxidant activity with no sign of toxicity. The antidiabetic effect of the plant could be due to the synergistic effect of various classes of constituents present in the root part of the plant.