Displaying publications 1 - 20 of 374 in total

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  1. Synthesis, Kinetics and Computational Explorations of 4-Phenylpiperazine Bearing N-(Aryl)-3-substituted-benzamides as Auspicious Tyrosinase Inhibitors
    Zeb A, Abbasi MA, Aziz-Ur-Rehman, Siddiqui SZ, Hassan M, Javed Q, et al.
    Chem Biodivers, 2024 Apr;21(4):e202400133.
    PMID: 38363553 DOI: 10.1002/cbdv.202400133
    In the aimed research study, a new series of N-(aryl)-3-[(4-phenyl-1-piperazinyl)methyl]benzamides was synthesized, which was envisaged as tyrosinase inhibitor. The structures of these newly designed molecules were verified by IR, 1H-NMR, 13C-NMR, EI-MS and CHN analysis data. These molecules were screened against tyrosinase and their inhibitory activity explored that these 3-substituted-benzamides exhibit good to excellent potential, comparative to the standard. The Kinetics mechanism was investigated through Lineweaver-Burk plots which depicted that molecules inhibited this enzyme in a competitive mode. Moreover, molecular docking was also performed to determine the binding interaction of all synthesized molecules (ligands) with the active site of tyrosinase enzyme and the results showed that most of the ligands exhibited efficient binding energy values. Therefore, it is anticipated that these molecules might serve as auspicious therapeutic scaffolds for treatment of the tyrosinase associated skin disorders.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology; Enzyme Inhibitors/chemistry
  2. Antimicrobial resistance in aquaculture: Occurrence and strategies in Southeast Asia
    Suyamud B, Chen Y, Quyen DTT, Dong Z, Zhao C, Hu J
    Sci Total Environ, 2024 Jan 10;907:167942.
    PMID: 37863226 DOI: 10.1016/j.scitotenv.2023.167942
    Aquaculture is a highly important and expanding industry in Southeast Asia (SEA). An upcoming problem is the emergence of antibiotic resistant pathogens due to the unchecked use of antibiotics and human clinical practices. This review focused insight into the occurrence of antimicrobial resistance (AMR) and strategies from SEA aquaculture based on the original research publication over the period 2002 to 2023. Amongst the 11 SEA countries, the most AMR report has come from Vietnam, Malaysia, and Thailand, respectively. The AMR found in SEA aquaculture were classified into 17 drug classes. The most reported AMR are aminoglycosides, beta-lactams, (fluoro)quinolones, tetracycline, sulpha group and multi-drug. Beta-lactams, tetracycline, sulpha group are reported in each country with the reported frequencies higher than 40 %. Escherichia coli, Aeromonas and Vibrio are the most widely and frequently reported ARB in SEA aquaculture. Multiple antibiotic resistance (MAR) indexes for the sample containing multiple bacterial isolates were generally low, while the medium numbers of MAR indexes for the typical bacteria species were higher than 0.2 and showed higher MAR levels than the global mean. Most of the detected ARGs are related to beta-lactams, tetracycline, sulpha group, and aminoglycosides. Amongst the beta-lactam resistance genes, blaTEM, and blaSHV are the most frequently detected. Almost all the available information of antibiotics, ARB and ARGs in SEA aquaculture was consistent with the global scale analysis. In addition, factors that contribute to the development and spread of AMR in SEA aquaculture were discussed. Moreover, the national action plan to combat AMR in SEA countries and the available technologies that already applied in the SEA aquaculture are also included in this review. Such findings underline the need for synergistic efforts from scientists, engineers, policy makers, government managers, entrepreneurs, and communities to manage and reduce the burden of AMR in aquaculture of SEA countries.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors
  3. Fulltext Fate and transport modelling for evaluating antibiotic resistance in aquatic environments: Current knowledge and research priorities
    Jampani M, Mateo-Sagasta J, Chandrasekar A, Fatta-Kassinos D, Graham DW, Gothwal R, et al.
    J Hazard Mater, 2024 Jan 05;461:132527.
    PMID: 37788551 DOI: 10.1016/j.jhazmat.2023.132527
    Antibiotics have revolutionised medicine in the last century and enabled the prevention of bacterial infections that were previously deemed untreatable. However, in parallel, bacteria have increasingly developed resistance to antibiotics through various mechanisms. When resistant bacteria find their way into terrestrial and aquatic environments, animal and human exposures increase, e.g., via polluted soil, food, and water, and health risks multiply. Understanding the fate and transport of antibiotic resistant bacteria (ARB) and the transfer mechanisms of antibiotic resistance genes (ARGs) in aquatic environments is critical for evaluating and mitigating the risks of resistant-induced infections. The conceptual understanding of sources and pathways of antibiotics, ARB, and ARGs from society to the water environments is essential for setting the scene and developing an appropriate framework for modelling. Various factors and processes associated with hydrology, ecology, and climate change can significantly affect the fate and transport of ARB and ARGs in natural environments. This article reviews current knowledge, research gaps, and priorities for developing water quality models to assess the fate and transport of ARB and ARGs. The paper also provides inputs on future research needs, especially the need for new predictive models to guide risk assessment on AR transmission and spread in aquatic environments.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors
  4. Methyl 4-pyridyl ketone thiosemicarbazone (4-PT) as an effective and safe inhibitor of mushroom tyrosinase and antibrowning agent
    Hassanuddin NA, Normaya E, Ismail H, Iqbal A, Piah MBM, Abd Hamid S, et al.
    Int J Biol Macromol, 2024 Jan;255:128229.
    PMID: 37981274 DOI: 10.1016/j.ijbiomac.2023.128229
    Enzymatic browning is of concern as it can affect food safety and quality. In this study, an effective and safe tyrosinase inhibitor and anti-browning agent, methyl 4-pyridyl ketone thiosemicarbazone (4-PT), was synthesised and characterised using Fourier-transform infrared (FTIR) spectroscopy, CHNS elemental analysis, and proton (1H) and carbon-13 (13C) nuclear magnetic resonance (NMR) spectroscopy. The vibrational frequencies of 4-PT were studied theoretically using vibrational energy distribution analysis (VEDA). Density functional theory (DFT) was applied to elucidate its chemical properties, including the Mulliken atomic charges, molecular electrostatic potential (MEP), quantum theory of atoms in molecules (QTAIM) and reduced density gradient non-covalent interactions (RDG-NCIs). Moreover, 4-PT was compared with kojic acid in terms of its effectiveness as a tyrosinase inhibitor and anti-browning agent. The toxicity and physicochemical properties of 4-PT were predicted via ADME evaluation, which proved that 4-PT is safer than kojic acid. Experimentally, 4-PT (IC50 = 5.82 μM, browning index (10 days) = 0.292 ± 0.002) was proven to be an effective tyrosinase inhibitor and anti-browning agent compared to kojic acid (IC50 = 128.17 μM, browning index (10 days) = 0.332 ± 0.002). Furthermore, kinetic analyses indicated that the type of tyrosinase inhibition is a mixed inhibition, with Km and Vmax values of 0.85 mM and 2.78 E-09 μM/s, respectively. Finally, the mechanism of 4-PT for tyrosinase inhibition was proven by 1D, second derivative and 2D IR spectroscopy, molecular docking and molecular dynamic simulation approaches.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology; Enzyme Inhibitors/chemistry
  5. Fulltext Knowledge, attitudes, and practices regarding antibiotic use and resistance among health science and non-health science university students in Thailand
    Precha N, Sukmai S, Hengbaru M, Chekoh M, Laohaprapanon S, Makkaew P, et al.
    PLoS One, 2024;19(1):e0296822.
    PMID: 38180959 DOI: 10.1371/journal.pone.0296822
    Antibiotic-resistant bacteria (ARB) have been recognized as one of the global health issues affecting humans, animals, and the environment. A lack of knowledge, negative attitudes, and irrational drug use can make significant contributions to the spread of ARB. This study aimed to assess the knowledge, attitudes, and practices (KAP) regarding antibiotic use and resistance among health science (HS) and non-health science (NHS) students and to determine the factors that influence their KAP concerning antibiotic use and resistance. A cross-sectional study was conducted among 404 HS and NHS students in Southern Thailand from December 2021 to March 2022. The students who fulfilled the study inclusion criteria responded to a questionnaire that had five dimensions. Descriptive statistics were used to analyze the qualitative variables, and Fisher's exact test was applied to compare the demographic variables, KAP responses between the HS and NHS students. The KAP regarding antibiotic use and resistance for each variable were compared using the Mann-Whitney U test and Kruskal-Wallis H test. Spearman's correlation test was used to estimate the correlation between the variables and KAP. A total of 404 (HS,162; NHS,242) students completed the self-administered questionnaire. The students' highest score was for attitude, followed by practice and knowledge. Our findings revealed that the HS students had higher levels of KAP correlated with antibiotic use and resistance than the NHS students (P < 0.001). The higher KAP scores were among the more senior students, which indicates that instruction on antibiotics was effective in their curriculum. Antibiotic use and resistance knowledge and attitudes should be conveyed to all university students via academic curriculum. Such interventions could set the standard for rational antibiotic use as well as long-term prevention and control of antibiotic-resistant bacteria.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors
  6. Economic Evaluations of Guideline-Directed Medical Therapies for Heart Failure With Reduced Ejection Fraction: A Systematic Review
    Kuan WC, Sim R, Wong WJ, Dujaili J, Kasim S, Lee KK, et al.
    Value Health, 2023 Oct;26(10):1558-1576.
    PMID: 37236395 DOI: 10.1016/j.jval.2023.05.011
    OBJECTIVES: Decision-analytic models (DAMs) with varying structures and assumptions have been applied in economic evaluations (EEs) to assist decision making for heart failure with reduced ejection fraction (HFrEF) therapeutics. This systematic review aimed to summarize and critically appraise the EEs of guideline-directed medical therapies (GDMTs) for HFrEF.

    METHODS: A systematic search of English articles and gray literature, published from January 2010, was performed on databases including MEDLINE, Embase, Scopus, NHSEED, health technology assessment, Cochrane Library, etc. The included studies were EEs with DAMs that compared the costs and outcomes of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, angiotensin-receptor neprilysin inhibitors, beta-blockers, mineralocorticoid-receptor agonists, and sodium-glucose cotransporter-2 inhibitors. The study quality was evaluated using the Bias in Economic Evaluation (ECOBIAS) 2015 checklist and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklists.

    RESULTS: A total of 59 EEs were included. Markov model, with a lifetime horizon and a monthly cycle length, was most commonly used in evaluating GDMTs for HFrEF. Most EEs conducted in the high-income countries demonstrated that novel GDMTs for HFrEF were cost-effective compared with the standard of care, with the standardized median incremental cost-effectiveness ratio (ICER) of $21 361/quality-adjusted life-year. The key factors influencing ICERs and study conclusions included model structures, input parameters, clinical heterogeneity, and country-specific willingness-to-pay threshold.

    CONCLUSIONS: Novel GDMTs were cost-effective compared with the standard of care. Given the heterogeneity of the DAMs and ICERs, alongside variations in willingness-to-pay thresholds across countries, there is a need to conduct country-specific EEs, particularly in low- and middle-income countries, using model structures that are coherent with the local decision context.

    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use
  7. Synthesis and Computational Exploration of Morpholine Bearing Halogenated Sulfonamides as Potential Tyrosinase Inhibitors
    Abbasi MA, Raza H, Aziz-Ur-Rehman, Siddiqui SZ, Muhammad S, Khan FM, et al.
    Chem Biodivers, 2023 Sep;20(9):e202300257.
    PMID: 37578300 DOI: 10.1002/cbdv.202300257
    In the presented work, a new series of three different 4-((3,5-dichloro-2-[(2/4-halobenzyl)oxy]phenyl)sulfonyl)morpholines was synthesized and the structure of these compounds were corroborated by 1 H-NMR & 13 C-NMR studies. The in vitro results established all the three compounds as potent tyrosinase inhibitors relative to the standard. The Kinetics mechanism plots established that compound 8 inhibited the enzyme non-competitively. The inhibition constants Ki calculated from Dixon plots for this compound was 0.0025 μM. Additionally, computational techniques were used to explore electronic structures of synthesized compounds. Fully optimized geometries were further docked with tyrosinase enzyme for inhibition studies. Reasonably good binding/interaction energies and intermolecular interactions were obtained. Finally, drug likeness was also predicted using the rule of five (RO5) and Chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics. It is anticipated that current experimental and computational investigations will evoke the scientific interest of the research community for the above-entitled compounds.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology; Enzyme Inhibitors/chemistry
  8. Fulltext RAAS inhibitors in COVID-19: They are not all the same!
    Kow CS, Ramachandram DS, Hasan SS
    Rev Port Cardiol, 2023 Sep;42(9):815-816.
    PMID: 37353197 DOI: 10.1016/j.repc.2023.04.008
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use
  9. Fulltext Is It Still Relevant to Discover New ACE Inhibitors from Natural Products? YES, but Only with Comprehensive Approaches to Address the Patients' Real Problems: Chronic Dry Cough and Angioedema
    Manoharan S
    Molecules, 2023 Jun 02;28(11).
    PMID: 37299008 DOI: 10.3390/molecules28114532
    Despite many publications related to the identification of new angiotensin-I-converting enzyme (ACE) inhibitors, especially peptides from natural products, the actual reason/s for why new ACE inhibitors need to be discovered are yet to be fully understood. New ACE inhibitors are pivotal to address serious side effects caused by commercially available ACE inhibitors in hypertensive patients. Despite the effectiveness of commercial ACE inhibitors, due to these side effects, doctors often prescribe angiotensin receptor blockers (ARBs). Recent evidence has shown the benefits of ACE inhibitors over ARBs in hypertensive patients and hypertensive-diabetes mellitus patients. In order to address these side effects, the somatic ACE's enzyme structures need to be revisited. The peptides isolated from the natural products need to be verified for their stability against ACE and several important gastrointestinal enzymes. The stable peptides sequence with the presence of favourable ACE inhibitory-related amino-acids, such as tryptophan (W), at the C-terminal need to be subjected to molecular docking and dynamics analyses for selecting ACE inhibitory peptide/s with C-domain-specific inhibition instead of both C- and N-domains' inhibition. This strategy will help to reduce the accumulation of bradykinin, the driving factor behind the formation of the side effects.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/adverse effects; Angiotensin-Converting Enzyme Inhibitors/chemistry
  10. Exploring chromone sulfonamides and sulfonylhydrazones as highly selective ectonucleotidase inhibitors: Synthesis, biological evaluation and in silico study
    Younus HA, Saeed M, Mahmood A, Jadoon MSK, Hameed A, Asari A, et al.
    Bioorg Chem, 2023 May;134:106450.
    PMID: 36924652 DOI: 10.1016/j.bioorg.2023.106450
    Ectonucleotidases, a well-known superfamily of plasma membrane located metalloenzymes plays a central role in mediating the process of purinergic cell signaling. Major functions performed by these enzymes include the hydrolysis of extracellular nucleosides and nucleotides which are considered as important cell-signaling molecules. Any (patho)-physiologically induced disruption in this purinergic cell signaling leads to several disorders, hence these enzymes are important drug targets for therapeutic purposes. Among the major challenges faced in the design of inhibitors of ectonucleotidases, an important one is the lack of selective inhibitors. Access to highly selective inhibitors via a facile synthetic route will not only be beneficial therapeutically, but will also lead to an increase in our understanding of intricate interplay between members of ectonucleotidase enzymes in relation to their selective activation and/or inhibition in different cells and tissues. Herein we describe synthesis of highly selective inhibitors of human intestinal alkaline phosphatase (h-IAP) and human tissue non-specific alkaline phosphatase (h-TNAP), containing chromone sulfonamide and sulfonylhydrazone scaffolds. Compound 1c exhibited highest (and most selective) h-IAP inhibition activity (h-IAP IC50 = 0.51 ± 0.20 µM; h-TNAP = 36.5%) and compound 3k showed highest activity and selective inhibition against h-TNAP (h-TNAP IC50 = 1.41 ± 0.10 µM; h-IAP = 43.1%). These compounds were also evaluated against another member of ectonucleotidase family, that is rat and human ecto-5'-nucleotidase (r-e5'NT and h-e5'NT). Some of the compounds exhibited excellent inhibitory activity against ecto-5'-nucleotidase. Compound 2 g exhibited highest inhibition against h-e5'NT (IC50 = 0.18 ± 0.02 µM). To rationalize the interactions with the binding site, molecular docking studies were carried out.
    Matched MeSH terms: Enzyme Inhibitors/chemistry
  11. 2-Aminothiazole-Oxadiazole Bearing N-Arylated Butanamides: Convergent Synthesis, Tyrosinase Inhibition, Kinetics, Structure-Activity Relationship, and Binding Conformations
    Raza H, Rehman Sadiq Butt A, Athar Abbasi M, Aziz-Ur-Rehman, Zahra Siddiqui S, Hassan M, et al.
    Chem Biodivers, 2023 Feb;20(2):e202201019.
    PMID: 36597268 DOI: 10.1002/cbdv.202201019
    A multi-step synthesis of novel bi-heterocyclic N-arylated butanamides was consummated through a convergent strategy and the structures of these medicinal scaffolds, 7a-h, were corroborated using spectral techniques. The in vitro analysis of these hybrid molecules revealed their potent tyrosinase inhibition as compared to the standard used. The kinetics mechanism was investigated through Lineweaver-Burk plots which exposed that, 7f, inhibited tyrosinase enzyme non-competitively by forming the enzyme-inhibitor complex. The inhibition constants Ki calculated from Dixon plots for this compound was 0.025 μM. Their binding conformations were ascertained by in silico computational studies whereby these molecules disclosed good binding energy values (kcal/mol). So, it was anticipated from the current research that these bi-heterocyclic butanamides might be probed as imperative therapeutic agents for melanogenesis.
    Matched MeSH terms: Enzyme Inhibitors/chemistry
  12. The Potential of Mur Enzymes as Targets for Antimicrobial Drug Discovery
    Kumar D, Sarkar N, Roy KK, Bisht D, Kumar D, Mandal B, et al.
    Curr Drug Targets, 2023;24(8):627-647.
    PMID: 37291783 DOI: 10.2174/1389450124666230608150759
    The extensive development in the strains of resistant bacteria is a potential hazard to public health worldwide. This necessitates the development of newer agents with the antibacterial property having new mechanisms of action. Mur enzymes catalyze the steps related to the biosynthesis of peptidoglycan, which constitutes a major part of the cell wall in bacteria. Peptidoglycan increases the stiffness of the cell wall, helping it to survive in unfavorable conditions. Therefore, the inhibition of Mur enzymes may lead to novel antibacterial agents that may help in controlling or overcoming bacterial resistance. Mur enzymes are classified into MurA, MurB, MurC, MurD, MurE, and MurF. Until-date, multiple inhibitors are reported for each class of the Mur enzymes. In this review, we have summarized the development of Mur enzyme inhibitors as antibacterial agents in the last few decades.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology; Enzyme Inhibitors/therapeutic use
  13. Fulltext Application of antimicrobial, potential hazard and mitigation plans
    Khoo SC, Goh MS, Alias A, Luang-In V, Chin KW, Ling Michelle TH, et al.
    Environ Res, 2022 Dec;215(Pt 1):114218.
    PMID: 36049514 DOI: 10.1016/j.envres.2022.114218
    The tremendous rise in the consumption of antimicrobial products had aroused global concerns, especially in the midst of pandemic COVID-19. Antimicrobial resistance has been accelerated by widespread usage of antimicrobial products in response to the COVID-19 pandemic. Furthermore, the widespread use of antimicrobial products releases biohazardous substances into the environment, endangering the ecology and ecosystem. Therefore, several strategies or measurements are needed to tackle this problem. In this review, types of antimicrobial available, emerging nanotechnology in antimicrobial production and their advanced application have been discussed. The problem of antimicrobial resistance (AMR) due to antibiotic-resistant bacteria (ARB)and antimicrobial resistance genes (AMG) had become the biggest threat to public health. To deal with this problem, an in-depth discussion of the challenges faced in antimicrobial mitigations and potential alternatives was reviewed.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors
  14. Fulltext Can Renin-Angiotensin System Inhibitors Protect Against Acute Kidney Injury in Patients With COVID-19?
    Kow CS, Ramachandram DS, Hasan SS
    Crit Care Med, 2022 Nov 01;50(11):e796-e797.
    PMID: 36227048 DOI: 10.1097/CCM.0000000000005618
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/pharmacology; Angiotensin-Converting Enzyme Inhibitors/therapeutic use
  15. Fulltext Outcomes of guideline-based medical therapy in patients with acute heart failure and reduced left ventricular ejection fraction: Observations from the Gulf acute heart failure registry (Gulf CARE)
    Jan RK, Alsheikh-Ali A, Mulla AA, Sulaiman K, Panduranga P, Al-Mahmeed W, et al.
    Medicine (Baltimore), 2022 Jun 10;101(23):e29452.
    PMID: 35687781 DOI: 10.1097/MD.0000000000029452
    This study aimed to report on the use, predictors and outcomes of guideline-based medical therapy (GBMT) in patients with acute heart failure (HF) with reduced ejection fraction of <40% (HFrEF), from seven countries in the Arabian Gulf.Patients with acute HFrEF (N = 2680), aged 18 years or older, and hospitalized February-November 2012 were recruited and data were collected post discharge at 3 months (n = 2477) and 1 year (n = 2418). The use and doses of GBMT were evaluated as per European, American and Canadian HF guidelines. Analyses were performed using multivariate logistic regression. This study was registered at clinicaltrials.gov (NCT01467973).The majority of patients were on dual (39%) and triple (39%) GBMT modalities, 14% received one GBMT medication, while 7.2% were not on any GBMT medications. On admission, 80% of patients were on renin-angiotensin system (RAS) blockers, 75% on b-blockers and 56% on mineralocorticoid receptor antagonists (MRAs), with a small proportion of these patients were taking target doses (RAS blockers 13%, b-blockers 7.3%, MRAs 14%). Patients taking triple GBMT were younger (P 
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use
  16. Fulltext Neuraminidase Inhibitor of Garcinia atroviridis L. Fruits and Leaves Using Partial Purification and Molecular Characterization
    Muchtaridi M, Nuwarda RF, Ikram EHK, Abdul Rahim AS, Gazzali AM, Wahab HA
    Molecules, 2022 Jan 30;27(3).
    PMID: 35164214 DOI: 10.3390/molecules27030949
    Neuraminidase (NA) is an enzyme that prevents virions from aggregating within the host cell and promotes cell-to-cell spread by cleaving glycosidic linkages to sialic acid. The best-known neuraminidase is the viral neuraminidase, which present in the influenza virus. Thus, the development of anti-influenza drugs that inhibit NA has emerged as an important and intriguing approach in the treatment of influenza. Garcinia atroviridis L. (GA) dried fruits (GAF) are used commercially as seasoning and in beverages. The main objective of this study was to identify a new potential neuraminidase inhibitor from GA. A bioassay-guided fractionation method was applied to obtain the bioactive compounds leading to the identification of garcinia acid and naringenin. In an enzyme inhibition study, garcinia acid demonstrated the highest activity when compared to naringenin. Garcinia acid had the highest activity, with an IC50 of 17.34-17.53 µg/mL or 91.22-92.21 µM against Clostridium perfringens-NA, and 56.71-57.85 µg/mL or 298.32-304.31 µM against H1N1-NA. Based on molecular docking results, garcinia acid interacted with the triad arginine residues (Arg118, Arg292, and Arg371) of the viral neuraminidase, implying that this compound has the potential to act as a NA enzyme inhibitor.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology*
  17. Fulltext Pharmaceutical Potential of Casein-Derived Tripeptide Met-Lys-Pro: Improvement in Cognitive Impairments and Suppression of Inflammation in APP/PS1 Mice
    Matsuzaki Tada A, Hamezah HS, Pahrudin Arrozi A, Abu Bakar ZH, Yanagisawa D, Tooyama I
    J Alzheimers Dis, 2022;89(3):835-848.
    PMID: 35964178 DOI: 10.3233/JAD-220192
    BACKGROUND: Tripeptide Met-Lys-Pro (MKP), a component of casein hydrolysates, has effective angiotensin-converting enzyme (ACE) inhibitory activity. Brain angiotensin II enzyme activates the NADPH oxidase complex via angiotensin II receptor type 1 (AT1) and enhances oxidative stress injury. ACE inhibitors improved cognitive function in Alzheimer's disease (AD) mouse models and previous clinical trials. Thus, although undetermined, MKP may be effective against pathological amyloid-β (Aβ) accumulation-induced cognitive impairment.

    OBJECTIVE: The current study aimed to investigate the potential of MKP as a pharmaceutical against AD by examining MKP's effect on cognitive function and molecular changes in the brain using double transgenic (APP/PS1) mice.

    METHODS: Experimental procedures were conducted in APP/PS1 mice (n = 38) with a C57BL/6 background. A novel object recognition test was used to evaluate recognition memory. ELISA was used to measure insoluble Aβ40, Aβ42, and TNF-α levels in brain tissue. Immunohistochemical analysis allowed the assessment of glial cell activation in MKP-treated APP/PS1 mice.

    RESULTS: The novel object recognition test revealed that MKP-treated APP/PS1 mice showed significant improvement in recognition memory. ELISA of brain tissue showed that MKP significantly reduced insoluble Aβ40, Aβ42, and TNF-α levels. Immunohistochemical analysis indicated the suppression of the marker for microglia and reactive astrocytes in MKP-treated APP/PS1 mice.

    CONCLUSION: Based on these results, we consider that MKP could ameliorate pathological Aβ accumulation-induced cognitive impairment in APP/PS1 mice. Furthermore, our findings suggest that MKP potentially contributes to preventing cognitive decline in AD.

    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use
  18. Quantitative microbiological risk assessment of complex microbial community in Prawn farm wastewater and applicability of nanoparticles and probiotics for eliminating of antibiotic-resistant bacteria
    Noman E, Al-Gheethi A, Radin Mohamed RMS, Talip B, Al-Sahari M, Al-Shaibani M
    J Hazard Mater, 2021 10 05;419:126418.
    PMID: 34171673 DOI: 10.1016/j.jhazmat.2021.126418
    The current review highlighted the quantitative microbiological risk assessment of Vibrio parahaemolyticus in Prawn farm wastewaters (PFWWs) and the applicability of nanoparticles for eliminating antibiotic-resistant bacteria (ARB). The high availability of the antibiotics in the environment and their transmission into human through the food-chain might cause unknown health effects. The aquaculture environments are considered as a reservoir for the antibiotic resistance genes (ARGs) and contributed effectively in the increasing of ABR. The metagenomic analysis is used to explore ARGs in the non-clinical environment. V. parahaemolyticus is among the pathogenic bacteria which are transmitted through sea food causing human acute gastroenteritis due to available thermostable direct hemolysin (tdh), adhesins, TDH related hemolysin (trh). The inactivation of pathogenic bacteria using nanoparticles act by disturbing the cell membrane, interrupting the transport system, DNA and mitochondria damage, and oxidizing the cellular component by reactive oxygen species (ROS). The chloramphenicol, nitrofurans, and nitroimidazole are among the prohibited drugs in fish and fishery product. The utilization of probiotics is the most effective and safe alternative for antibiotics in Prawn aquaculture. This review will ensure public understanding among the readers on how they can decrease the risk of the antimicrobial resistance distribution in the environment.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors
  19. Forrestiacids A and B, Pentaterpene Inhibitors of ACL and Lipogenesis: Extending the Limits of Computational NMR Methods in the Structure Assignment of Complex Natural Products
    Xiong J, Zhou PJ, Jiang HW, Huang T, He YH, Zhao ZY, et al.
    Angew Chem Int Ed Engl, 2021 Oct 04;60(41):22270-22275.
    PMID: 34374477 DOI: 10.1002/anie.202109082
    Forrestiacids A (1) and B (2) are a novel class of [4+2] type pentaterpenoids derived from a rearranged lanostane moiety (dienophile) and an abietane unit (diene). These unprecedented molecules were isolated using guidance by molecular ion networking (MoIN) from Pseudotsuga forrestii, an endangered member of the Asian Douglas Fir Family. The intermolecular hetero-Diels-Alder adducts feature an unusual bicyclo[2.2.2]octene ring system. Their structures were elucidated by spectroscopic analysis, GIAO NMR calculations and DP4+ probability analyses, electronic circular dichroism calculations, and X-ray diffraction analysis. This unique addition to the pentaterpene family represents the largest and the most complex molecule successfully assigned using computational approaches to predict accurately chemical shift values. Compounds 1 and 2 exhibited potent inhibitory activities (IC50 s <5 μM) of ATP-citrate lyase (ACL), a new drug target for the treatment of glycolipid metabolic disorders including hyperlipidemia. Validating this activity 1 effectively attenuated the de novo lipogenesis in HepG2 cells. These findings provide a new chemical class for developing potential therapeutic agents for ACL-related diseases with strong links to traditional medicines.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology*; Enzyme Inhibitors/chemistry
  20. Synthesis, in vitro antiurease, in vivo antinematodal activity of quinoline analogs and their in-silico study
    Zaman K, Rahim F, Taha M, Sajid M, Hayat S, Nawaz M, et al.
    Bioorg Chem, 2021 10;115:105199.
    PMID: 34329995 DOI: 10.1016/j.bioorg.2021.105199
    Synthesis of quinoline analogs and their urease inhibitory activities with reference to the standard drug, thiourea (IC50 = 21.86 ± 0.40 µM) are presented in this study. The inhibitory activity range is (IC50 = 0.60 ± 0.01 to 24.10 ± 0.70 µM) which displayed that it is most potent class of urease inhibitor. Analog 1-9, and 11-13 emerged with many times greater antiurease potential than thiourea, in which analog 1, 2, 3, 4, 8, 9, and 11 (IC50 = 3.50 ± 0.10, 7.20 ± 0.20, 1.30 ± 0.10, 2.30 ± 0.10, 0.60 ± 0.01, 1.05 ± 0.10 and 2.60 ± 0.10 µM respectively) were appeared the most potent ones among the series. In this context, most potent analogs such as 1, 3, 4, 8, and 9 were further subjected for their in vitro antinematodal study against C. elegans to examine its cytotoxicity under positive control of standard drug, Levamisole. Consequently, the cytotoxicity profile displayed that analogs 3, 8, and 9 were found with minimum cytotoxic outline at higher concentration (500 µg/mL). All analogs were characterized through 1H NMR, 13C NMR and HR-EIMS. The protein-ligand binding interaction for most potent analogs was confirmed via molecular docking study.
    Matched MeSH terms: Enzyme Inhibitors/chemical synthesis; Enzyme Inhibitors/pharmacology*; Enzyme Inhibitors/chemistry
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