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Naeem Ur Rehman,1 Mariya al-Rashida,2 Ahmed Tokhi,1 Zainab Ahmed,1 Fazal Subhan,1 Muzaffar Abbas,3 Muhammad Awais Arshid,4 Khalid Rauf1 1Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, Pakistan; 2Department of Chemistry, Forman Christian College (A Chartered University), Lahore 54600, Pakistan; 3Department of Pharmacy, Capital University of Science and Technology (CUST), Islamabad, Pakistan; 4Aga Khan University Karachi, Karachi, PakistanCorrespondence: Khalid Rauf Tel + (92) 345 9824468Email khalidrauf@cuiatd.edu.pkIntroduction: 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 5HT3 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.Keywords: sulfonamides, streptozotocin; STZ, antinociception, diabetes mellitus; DM, neuropathic pain, von Frey filaments

Naeem Ur Rehman,1 Muzaffar Abbas,2 Mariya al-Rashida,3 Ahmed Tokhi,1 Muhammad Awais Arshid,4 Muhammad Sona Khan,1 Izhar Ahmad,1 Khalid Rauf1 1Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Islamabad, Pakistan; 2Department of Pharmacy, Capital University of Science and Technology (CUST), Islamabad, Pakistan; 3Department of Chemistry, Forman Christian College (A Chartered University), Lahore 54600, Pakistan; 4Aga Khan University, Karachi, PakistanCorrespondence: Khalid Rauf Tel +92 345 9824468Email khalidrauf@cuiatd.edu.pkIntroduction: 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.Keywords: 4-fluoro-N-(4-sulfamoylbenzyl) benzene-sulfonamide (4-FBS), nicotine sensitization, pharmacotherapy, drug addiction, locomotor activity, adenosine, HPLC

Umar Farooq,1,* Touqeer Ahmad,1,* Ajmal Khan,2 Rizwana Sarwar,1 Jazib Shafiq,3 Yasir Raza,4 Ayaz Ahmed,3 Safi Ullah,5 Najeeb Ur Rehman,2 Ahmed Al-Harrasi21Department of Chemistry, COMSATS University Islamabad Abbottabad Campus, Abbottabad, Pakistan; 2Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Sultanate of Oman; 3Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan; 4Department of Microbiology, University of Karachi, Karachi, Pakistan; 5Department of Pharmacy, University of Peshawar, Peshawar, Pakistan*These authors contributed equally to this workBackground: Infections caused by drug resistant bacteria are a major health concern worldwide and have prompted scientists to carry out efforts to overcome this challenge. Researchers and pharmaceutical companies are trying to develop new kinds of antimicrobial agents by using different physical and chemical methods to overcome these problems.Materials and methods: In the present study, rifampicin conjugated silver (Rif-Ag) nanoparticles have successfully been synthesized using a chemical method. Characterization of the nanoparticles was performed using a UV-Vis spectrophotometer, FTIR, SEM, TEM, and AFM.Results: The AFM, SEM, and TEM results showed that the average particle size of Rif-Ag nanoparticles was about 15–18±4 nm. The FTIR spectra revealed the conjugation of –NH2 and –OH functional moiety with silver nanoparticles surface. Considering the penetrating power of rifampicin, the free drug is compared with synthesized nanoparticle for antimicrobial, biofilm inhibition, and eradication potential. Synthesized nanoparticles were found to be significantly active as compared to drug alone.Conclusion: This study has shown greater biofilm inhibitory and eradicating potential against methicillin resistant Staphylococcus aureus and Klebsiella pneumoniae, as evident by crystal violet, MTT staining, and microscopic analysis. So, it will be further modified, and studies for the mechanism of action are needed.Keywords: rifampicin, silver nanoparticles, TEM, AFM, antibiofilm, Staphylococcus aureus, Klebsiella pneumoniae

Shaimaa Ahmed,1 Thirumala Govender,1 Inamullah Khan,2 Nisar ur Rehman,2 Waqar Ali,2 Syed Muhammad Hassan Shah,3 Shahzeb Khan,4 Zahid Hussain,5 Riaz Ullah,6,7 Mansour S Alsaid6 1Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa; 2Department of Pharmacy, COMSATS Institute of Information Technology (CIIT), Abbotabad, 3Department of Pharmacy, Sarhad University of Science and Technology, Peshawar, 4Department of Pharmacy, University of Malakand Dir (Lower), Chakdara, Khyber Pakhtunkhwa, Pakistan; 5Department of Pharmaceutics, Faculty of Pharmacy, Universiti Teknologi Mara, Puncak Alam, Selangor, Malaysia; 6Department of Pharmacognosy and Medicinal, Aromatic & Poisonous Plants Research Center (MAPPRC), College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 7Department of Chemistry, Government College Ara Khel FR, Kohat, Khyber Pakhtunkhwa, Pakistan Background and aim: The challenges with current antimicrobial drug therapy and resistance remain a significant global health threat. Nanodrug delivery systems are playing a crucial role in overcoming these challenges and open new avenues for effective antimicrobial therapy. While fluticasone (FLU), a poorly water-soluble corticosteroid, has been reported to have potential antimicrobial activity, approaches to optimize its dissolution profile and antimicrobial activity are lacking in the literature. This study aimed to combine an experimental study with molecular modeling to design stable FLU nanopolymeric particles with enhanced dissolution rates and antimicrobial activity. Methods: Six different polymers were used to prepare FLU nanopolymeric particles: hydroxyl propyl methylcellulose (HPMC), poly (vinylpyrrolidone) (PVP), poly (vinyl alcohol) (PVA), ethyl cellulose (EC), Eudragit (EUD), and Pluronics®. A low-energy method, nanoprecipitation, was used to prepare the polymeric nanoparticles. Results and conclusion: The combination of HPMC-PVP and EUD-PVP was found most effective to produce stable FLU nanoparticles, with particle sizes of 250 nm ±2.0 and 280 nm ±4.2 and polydispersity indices of 0.15 nm ±0.01 and 0.25 nm ±0.03, respectively. The molecular modeling studies endorsed the same results, showing highest polymer drug binding free energies for HPMC-PVP-FLU (-35.22 kcal/mol ±0.79) and EUD-PVP-FLU (-25.17 kcal/mol ±1.12). In addition, it was observed that Ethocel® favored a wrapping mechanism around the drug molecules rather than a linear conformation that was witnessed for other individual polymers. The stability studies conducted for 90 days demonstrated that HPMC-PVP-FLU nanoparticles stored at 2°C–8°C and 25°C were more stable. Crystallinity of the processed FLU nanoparticles was confirmed using differential scanning calorimetry, powder X-ray diffraction analysis and TEM. The Fourier transform infrared spectroscopy (FTIR) studies showed that there was no chemical interaction between the drug and chosen polymer system. The HPMC-PVP-FLU nanoparticles also showed enhanced dissolution rate (P

6-Methoxyflavone (6-MOF) is a flavonoid that has been reported to be a GABA-A receptor agonist and reverses cisplatin-induced hyperalgesia and allodynia. Considering the varied neuropharmacological profile of 6-MOF, this study was intended to determine the pharmacological effects of 6-MOF on locomotion, anxiety, novel object recognition (NOR), depression, spatial memory, socialization behavior, nest-building behavior, and depression in various groups of mice. Selected groups of mice were injected with 25, 50, and 75 mg/kg 6-MOF. Using HPLC-UV, the frontal cortex, striatum, and hippocampus of the sacrificed mice were analyzed for the levels of vitamin C, dopamine, serotonin, noradrenaline, adenosine, and its metabolites. Statistical analysis showed significant results in socialization behavior and elevated plus maze with 75 mg/kg. In Y-maze, NOR 6-MOF showed significant results at all three doses, while in tail suspension test (TST), 50 and 75 mg/kg showed significant results; however, no statistical significance was observed in nest-building behavior; 50 and 75 mg/kg 6-MOF showed significant results in the Morris water maze. 6-MOF raised vitamin C levels in the frontal cortex and hippocampus. Serotonin, dopamine, and nor-adrenaline levels were raised in the hippocampus and striatum. It has also imparted region-specific neuroprotection by improving adenosine and its metabolite levels. In silico studies performed using PyRx have shown that the minimum binding energy of 6-MOF with antioxidant enzyme is −7.1 k/cal/mol. The binding energy showed that 6-MOF was successfully docked with an anti-oxidant enzyme. In conclusion, in silico and behavioral studies showed that 6-MOF can be a potential candidate for the treatment of cognitive decline, anxiety, and depression.

Aims: To develop a pcsB‐based Loop‐mediated isothermal amplification (LAMP) method for the detection of Streptococcus agalactiae (GBS) in milk, tilapia and vaginal swabs. Methods and Results: The sensitivity of the LAMP method using real‐time turbidity monitoring was 1 pg of template within 1 h at 64°C, 100‐fold higher than conventional PCR. The sensitivity of visual detection dropped an order of magnitude using SYBR Green I or hydroxynaphthol blue. The validity of the visual LAMP assay was assessed by the detection of GBS in 180 vaginal swabs from one hospital, 14 brain tissues samples of diseased tilapias from two fishponds and fresh milk of 67 dairy cattle from one farm. In total, 17 samples (4 vaginal swabs, 13 tilapia brain tissues but no milk sample) tested positive for GBS. Subsequent bacterial identification confirmed the specificity and reliability of the LAMP method. Molecular serotyping and multilocus sequence typing demonstrated that all 13 tilapia GBS isolates were identical (serotype Ia, ST7), whereas the four human GBS isolates were more diverse and could be classified into two serotypes (Ia, III) and four sequence types (ST19, ST23, ST24, ST862). Virulence gene testing showed that only the bac, rib and lmb genes were not present in all isolates. Antimicrobial susceptibility profiles of the isolates were basically consistent with their genotypes, except for sulphonamide and fluoroquinolone. Conclusions: We developed a reliable pcsB‐based LAMP assay for GBS detection. Our results demonstrated that the prevalence of GBS was 92·9% among diseased tilapia, 2·2% among female patients and 0% on a dairy farm in Hainan. Significance and Impact of the Study: The pcsB‐based LAMP method is suitable for GBS detection and contains great potential of application in dairy industry, aquiculture and clinical. [ABSTRACT FROM AUTHOR]

The present paper's primary purpose is to study the connection between commutativity of rings and the behavior of its derivations in prime rings.

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.)

Introduction: Countries are grappling with a rapidly worsening upsurge in the opioid-related overdose deaths, misuse and abuse. There is a dearth of data in Pakistan regarding the practices and competencies of pharmacists in handling opioid-related issues., Study Design: A cross-sectional study, conducted across Punjab, Pakistan., Method: The study deployed a validated survey to evaluate the competencies and practices of the community and hospital pharmacists., Results: 504 community pharmacists and 279 hospital pharmacists participated in the survey with an overall response rate of 85.5%. Almost half of the respondents 'never' or 'sometimes' made clinical notes in a journal or dispensing software to monitor ongoing opioid use. Generally, pharmacists were reluctant to collaborate with physicians or notify police regarding the abuse/misuse of opioids. Hospital pharmacists achieved significantly higher mean competency scores than chain and independent community pharmacists (p<0.05). In competency evaluation, three priority areas emerged that require additional training, that is, 'opioid overdose management', 'opioid use monitoring' and 'therapeutic uses of opioids'., Conclusion: Both community and hospital pharmacists hold significant positions and potential to contribute meaningfully to the mitigation of harms and risks associated with opioids. Nevertheless, this study underscores notable deficiencies in the competence of pharmacists, whether in hospital or community settings in Punjab, concerning various aspects related to the dispensing and utilisation of opioids. It also highlights the pressing need for the development of strategies aimed at improving several practice areas including the documentation, the quality of patient counselling, the effectiveness of reporting mechanisms for opioid abuse and the stringent enforcement of regulatory policies to curtail opioid misuse. Thus, to mitigate the opioid epidemic in Pakistan, it is imperative to institute opioid stewardship initiatives aimed at rectifying the competency and procedural deficiencies within the pharmacist workforce., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

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.)

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.)

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.

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.

Background: Medical and pharmacy students are future healthcare professionals who will be on the forefront in dealing with antibiotics in hospitals or community settings. Whether the current medical and pharmacy education in Pakistan prepares students to take future roles in antibiotic use remains an under-researched area., Aim: This study aims to compare medical and pharmacy students' perceived preparedness, learning practices and usefulness of the education and training on antibiotic use and resistance imparted during undergraduate studies in Pakistan., Design and Setting: It was amulti-centre cross-sectional survey of medical and pharmacy colleges in Punjab, Pakistan., Method: A self-administered questionnaire was used to collect data from final year medical and pharmacy students. Descriptive statistics were used for categorical variables while independent t -test and One-way ANOVA computed group differences., Result: Nine hundred forty-eight respondents (526 medical and 422 pharmacy students) completed the survey from 26 medical and 19 pharmacy colleges. Majority (76.1%) of the pharmacy students had not completed a clinical rotation in infectious diseases. The top three most often used sources of learning antibiotic use and resistance were the same among the medical and the pharmacy students; included textbooks, Wikipedia, and smart phone apps. Overall self-perceived preparedness scores showed no significant difference between pharmacy and medical students. The least prepared areas by medical and pharmacy students included transition from intravenous to oral antibiotics and interpretation of antibiograms. Both medical and pharmacy students found problem solving sessions attended by a small group of students to be the most useful (very useful) teaching methodology to learn antibiotic use and resistance., Conclusions: Differences exist between medical and pharmacy students in educational resources used, topics covered during undergraduate degree. To curb the growing antibiotic misuse and resistance, the concerned authorities should undertake targeted educational reforms to ensure that future physicians and pharmacists can play a pivotal role in rationalizing the use of antibiotics.

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.)