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  1. Fulltext Recent advances in application of biosensors in tissue engineering
    Hasan A, Nurunnabi M, Morshed M, Paul A, Polini A, Kuila T, et al.
    Biomed Res Int, 2014;2014:307519.
    PMID: 25165697 DOI: 10.1155/2014/307519
    Biosensors research is a fast growing field in which tens of thousands of papers have been published over the years, and the industry is now worth billions of dollars. The biosensor products have found their applications in numerous industries including food and beverages, agricultural, environmental, medical diagnostics, and pharmaceutical industries and many more. Even though numerous biosensors have been developed for detection of proteins, peptides, enzymes, and numerous other biomolecules for diverse applications, their applications in tissue engineering have remained limited. In recent years, there has been a growing interest in application of novel biosensors in cell culture and tissue engineering, for example, real-time detection of small molecules such as glucose, lactose, and H2O2 as well as serum proteins of large molecular size, such as albumin and alpha-fetoprotein, and inflammatory cytokines, such as IFN-g and TNF-α. In this review, we provide an overview of the recent advancements in biosensors for tissue engineering applications.
    Matched MeSH terms: Antibodies/chemistry*; Enzymes/chemistry*; Quantum Dots/chemistry
  2. Fulltext Kinetics of molybdenum reduction to molybdenum blue by Bacillus sp. strain A.rzi
    Othman AR, Bakar NA, Halmi MI, Johari WL, Ahmad SA, Jirangon H, et al.
    Biomed Res Int, 2013;2013:371058.
    PMID: 24369531 DOI: 10.1155/2013/371058
    Molybdenum is very toxic to agricultural animals. Mo-reducing bacterium can be used to immobilize soluble molybdenum to insoluble forms, reducing its toxicity in the process. In this work the isolation of a novel molybdate-reducing Gram positive bacterium tentatively identified as Bacillus sp. strain A.rzi from a metal-contaminated soil is reported. The cellular reduction of molybdate to molybdenum blue occurred optimally at 4 mM phosphate, using 1% (w/v) glucose, 50 mM molybdate, between 28 and 30 °C and at pH 7.3. The spectrum of the Mo-blue product showed a maximum peak at 865 nm and a shoulder at 700 nm. Inhibitors of bacterial electron transport system (ETS) such as rotenone, sodium azide, antimycin A, and potassium cyanide could not inhibit the molybdenum-reducing activity. At 0.1 mM, mercury, copper, cadmium, arsenic, lead, chromium, cobalt, and zinc showed strong inhibition on molybdate reduction by crude enzyme. The best model that fitted the experimental data well was Luong followed by Haldane and Monod. The calculated value for Luong's constants p max, K(s), S(m), and n was 5.88 μmole Mo-blue hr(-1), 70.36 mM, 108.22 mM, and 0.74, respectively. The characteristics of this bacterium make it an ideal tool for bioremediation of molybdenum pollution.
    Matched MeSH terms: Bacillus/chemistry; Molybdenum/chemistry; Phosphates/chemistry
  3. Fulltext Chemistry, Biosynthesis, Physicochemical and Biological Properties of Rubiadin: A Promising Natural Anthraquinone for New Drug Discovery and Development
    Watroly MN, Sekar M, Fuloria S, Gan SH, Jeyabalan S, Wu YS, et al.
    Drug Des Devel Ther, 2021;15:4527-4549.
    PMID: 34764636 DOI: 10.2147/DDDT.S338548
    Anthraquinones (AQs) are found in a variety of consumer products, including foods, nutritional supplements, drugs, and traditional medicines, and have a wide range of pharmacological actions. Rubiadin, a 1,3-dihydroxy-2-methyl anthraquinone, primarily originates from Rubia cordifolia Linn (Rubiaceae). It was first discovered in 1981 and has been reported for many biological activities. However, no review has been reported so far to create awareness about this molecule and its role in future drug discovery. Therefore, the present review aimed to provide comprehensive evidence of Rubiadin's phytochemistry, biosynthesis, physicochemical properties, biological properties and therapeutic potential. Relevant literature was gathered from numerous scientific databases including PubMed, ScienceDirect, Scopus and Google Scholar between 1981 and up-to-date. The distribution of Rubiadin in numerous medicinal plants, as well as its method of isolation, synthesis, characterisation, physiochemical properties and possible biosynthesis pathways, was extensively covered in this review. Following a rigorous screening and tabulating, a thorough description of Rubiadin's biological properties was gathered, which were based on scientific evidences. Rubiadin fits all five of Lipinski's rule for drug-likeness properties. Then, the in depth physiochemical characteristics of Rubiadin were investigated. The simple technique for Rubiadin's isolation from R. cordifolia and the procedure of synthesis was described. Rubiadin is also biosynthesized via the polyketide and chorismate/o-succinylbenzoic acid pathways. Rubiadin is a powerful molecule with anticancer, antiosteoporotic, hepatoprotective, neuroprotective, anti-inflammatory, antidiabetic, antioxidant, antibacterial, antimalarial, antifungal, and antiviral properties. The mechanism of action for the majority of the pharmacological actions reported, however, is unknown. In addition to this review, an in silico molecular docking study was performed against proteins with PDB IDs: 3AOX, 6OLX, 6OSP, and 6SDC to support the anticancer properties of Rubiadin. The toxicity profile, pharmacokinetics and possible structural modifications were also described. Rubiadin was also proven to have the highest binding affinity to the targeted proteins in an in silico study; thus, we believe it may be a potential anticancer molecule. In order to present Rubiadin as a novel candidate for future therapeutic development, advanced studies on preclinical, clinical trials, bioavailability, permeability and administration of safe doses are necessary.
    Matched MeSH terms: Anthraquinones/chemistry; Antineoplastic Agents, Phytogenic/chemistry; Rubia/chemistry
  4. Discovery of indoleninyl-pyrazolo[3,4-b]pyridines as potent chemotherapeutic agents against colorectal cancer cells
    Basir NH, Ramle AQ, Ng MP, Tan CH, Tiekink ERT, Sim KS, et al.
    Bioorg Chem, 2024 May;146:107256.
    PMID: 38460334 DOI: 10.1016/j.bioorg.2024.107256
    A new series of indolenines decorated with pyrazolo[3,4-b]pyridines were designed and synthesized in up to 96% yield from the acid-catalyzed cyclocondensation of 1,3-dialdehydes with 3-aminopyrazoles. X-ray crystallography on a representative derivative, 5n, revealed two close to planar conformations whereby the N-atom of the pyridyl residue was syn or anti to the pyrrole-N atom in the two independent molecules of the asymmetric unit. The computational and DNA binding data suggest that 5n is a strong DNA intercalator with the results in agreement with its potent cytotoxicity against two colorectal cancer cell lines (HCT 116 and HT-29). In contrast to doxorubicin, compounds 5k-o have higher druggability (compliance to more criteria stated in Lipinski's rule of five and Veber's rule), higher bioavailability, and better medicinal chemistry properties, indicative of their potential application as chemotherapeutical agents.
    Matched MeSH terms: Indoles/chemistry; Pyrazoles/chemistry; Pyridines/chemistry
  5. Fulltext Structural studies of Chikungunya virus maturation
    Yap ML, Klose T, Urakami A, Hasan SS, Akahata W, Rossmann MG
    Proc Natl Acad Sci U S A, 2017 12 26;114(52):13703-13707.
    PMID: 29203665 DOI: 10.1073/pnas.1713166114
    Cleavage of the alphavirus precursor glycoprotein p62 into the E2 and E3 glycoproteins before assembly with the nucleocapsid is the key to producing fusion-competent mature spikes on alphaviruses. Here we present a cryo-EM, 6.8-Å resolution structure of an "immature" Chikungunya virus in which the cleavage site has been mutated to inhibit proteolysis. The spikes in the immature virus have a larger radius and are less compact than in the mature virus. Furthermore, domains B on the E2 glycoproteins have less freedom of movement in the immature virus, keeping the fusion loops protected under domain B. In addition, the nucleocapsid of the immature virus is more compact than in the mature virus, protecting a conserved ribosome-binding site in the capsid protein from exposure. These differences suggest that the posttranslational processing of the spikes and nucleocapsid is necessary to produce infectious virus.
    Matched MeSH terms: Chikungunya virus/chemistry*; Glycoproteins/chemistry*; Viral Envelope Proteins/chemistry*
  6. Fulltext Pharmaceutical pollution of the world's rivers
    Wilkinson JL, Boxall ABA, Kolpin DW, Leung KMY, Lai RWS, Galbán-Malagón C, et al.
    Proc Natl Acad Sci U S A, 2022 Feb 22;119(8).
    PMID: 35165193 DOI: 10.1073/pnas.2113947119
    Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals.
    Matched MeSH terms: Water/chemistry; Rivers/chemistry*; Waste Water/chemistry
  7. Fulltext Phenolic content, antioxidant effect and cytotoxic activity of Leea indica leaves
    Reddy NS, Navanesan S, Sinniah SK, Wahab NA, Sim KS
    BMC Complement Altern Med, 2012 Aug 17;12:128.
    PMID: 22898370 DOI: 10.1186/1472-6882-12-128
    BACKGROUND: The leaves of Leea indica (Vitaceae), commonly known as 'Huo Tong Shu' in Malaysia, have been traditionally used as natural remedy in folk medicine by the locals. The current study reports the outcome of antioxidant and cytotoxic investigation of L. indica leaves. To the best of our knowledge, this is the first report of L. indica leaf crude ethanol and its fractionated extracts (hexane, ethyl acetate and water) for evaluation of total phenolic content, antioxidant effect and cytotoxic activity against colon cancer cell lines.

    METHODS: In the present study, L. indica leaf crude ethanol and its fractionated extracts (hexane, ethyl acetate and water) were firstly prepared prior to phenolic content, antioxidant effect and cytotoxic activity assessment. Folin-Ciocalteau's method was used for the measurement of total phenolic content of the extracts. The antioxidant activity was measured by employing three different established testing systems, such as scavenging activity on DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals, reducing power assay and SOD (superoxide dismutase) activity assay. The cytotoxic activity of the extracts were evaluated against three colon cancer cell lines with varying molecular characteristics (HT-29, HCT-15 and HCT-116) by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay.

    RESULTS: The total phenolic content and antioxidant capabilities differed significantly among the L. indica leaf extracts. A strong correlation between total phenolic content and antioxidant properties was found, indicating that phenolic compounds are the major contributor to the antioxidant properties of these extracts. Among the crude ethanol and its fractionated extracts, fractionated water extract showed significantly the highest total phenolic content and strongest antioxidant effect in all the antioxidant testing systems employed in this study. All the four extracts exert no damage to the selected colon cancer cells.

    CONCLUSIONS: The data obtained in these testing systems clearly establish the antioxidant potency of the fractionated water extract of L. indica leaves. Additional studies should be carried out to isolate and identify the bioactive compounds in the fractionated water extract, in order to provide more convincing evidence.

    Matched MeSH terms: Plant Extracts/chemistry; Plant Leaves/chemistry; Vitaceae/chemistry*
  8. Fulltext Antibiofilm properties of chemically synthesized silver nanoparticles found against Pseudomonas aeruginosa
    Palanisamy NK, Ferina N, Amirulhusni AN, Mohd-Zain Z, Hussaini J, Ping LJ, et al.
    J Nanobiotechnology, 2014 Jan 14;12:2.
    PMID: 24422704 DOI: 10.1186/1477-3155-12-2
    Nanomedicine is now being introduced as a recent trend in the field of medicine. It has been documented that metal nanoparticles have antimicrobial effects for bacteria, fungi and viruses. Recent advances in technology has revived the use of silver nanoparticles in the medical field; treatment, diagnosis, monitoring and control of disease. It has been used since ancient times for treating wide range of illnesses. Bacterial cells adheres to surfaces and develop structures known as biofilms. These structures are natural survival strategy of the bacteria to invade the host. They are more tolerant to commonly used antimicrobial agents, thus being more difficult to be controlled. This leads to increase in severity of infection. In this study, we have investigated the effect of silver nanoparticles in the formation of biofilm in multidrug resistant strains of Pseudomonas aeruginosa. Observation showed that biofilm formation occurred at bacterial concentration of 10(6) cfu/ml for the sensitive strain of P. aeruginosa while in the resistant strain, the biofilm was evident at bacterial concentration of about 10(3) cfu/ml. The biofilm were then tested against various concentrations of silver nanoparticles to determine the inhibitory effect of the silver nanoparticles. In the sensitive strain, 20 μg/ml of silver nanoparticles inhibited the growth optimally at bacterial concentration of 10(4) cfu/ml with an inhibition rate of 67%. Similarly, silver nanoparticles inhibited the formation of biofilm in the resistant strain at an optimal bacterial concentration of 10(5) cfu/ml with an inhibition rate of 56%. Thus, silver nanoparticles could be used as a potential alternative therapy to reduce severity of disease due to P. aeruginosa infections.
    Matched MeSH terms: Anti-Bacterial Agents/chemistry; Silver/chemistry; Metal Nanoparticles/chemistry*
  9. Fulltext Granular Formation during Apoptosis in Blastocystis sp. Exposed to Metronidazole (MTZ)
    Dhurga DB, Suresh K, Tan TC
    PLoS One, 2016;11(7):e0155390.
    PMID: 27471855 DOI: 10.1371/journal.pone.0155390
    The role and function of the granular life cycle stage in Blastocystis sp, remains uncertain despite suggestions being made that the granules are metabolic, reproductive and lipid in nature. This present study aims to understand granular formation by triggering apoptosis in Blastocystis sp. by treating them with metronidazole (MTZ). Blastocystis sp.cultures of 4 sub-types namely 1, 2, 3 and 5 when treated with 0.01 and 0.0001 mg/ml of metronidazole (MTZ) respectively showed many of the parasites to be both viable and apoptotic (VA). Treated subtype 3 isolates exhibited the highest number of granular forms i.e. 88% (p<0.001) (0.0001 mg/ml) and 69% (p<0.01) (0.01 mg/ml) respectively at the 72 h in in vitro culture compared to other subtypes. These VA forms showed distinct granules using acridine orange (AO) and 4',6-diamino-2-phenylindole (DAPI) staining with a mean per cell ranging from 5 in ST 5 to as high as 16 in ST 3. These forms showed intact mitochondria in both viable apoptotic (VA) and viable non-apoptotic (VNA) cells with a pattern of accumulation of lipid droplets corresponding to viable cells. Granular VA forms looked ultra-structurally different with prominent presence of mitochondria-like organelle (MLO) and a changed mitochondrial trans-membrane potential with thicker membrane and a highly convoluted inner membrane than the less dense non-viable apoptotic (NVA) cells. This suggests that granular formation during apoptosis is a self-regulatory mechanism to produce higher number of viable cells in response to treatment. This study directs the need to search novel chemotherapeutic approaches by incorporating these findings when developing drugs against the emerging Blastocystis sp. infections.
    Matched MeSH terms: Acridine Orange/chemistry; Diamines/chemistry; Indoles/chemistry
  10. Fulltext Efficient chromium removal from leather industrial wastewater in batch experimental study: Green synthesis and characterization of zinc oxide nanoparticles using Ficus benghalensis extracts
    Irshad MA, Abdullah, Latif M, Nasim I, Nawaz R, Zahoor AF, et al.
    Ecotoxicol Environ Saf, 2024 Aug;281:116616.
    PMID: 38917589 DOI: 10.1016/j.ecoenv.2024.116616
    The urgent need to address the severe environmental risk posed by chromium-contaminated industrial wastewater necessitates the development of eco-friendly cleanup methodologies. Utilizing the Ficus benghalensis plant extracts, the present study aims to develop green zinc oxide nanoparticles for the removal of Cr metal ions from wastewater. The leaves of Ficus benghalensis, often known as the banyan tree, were used to extract a solution for synthesizing ZnO NPs. These nanoparticles were developed with the goal of efficiently eliminating chromium (Cr) from industrial effluents. Batch studies were carried out to assess the efficiency of these synthesized ZnO NPs in treating leather industrial effluent, with aiming for optimal chromium removal. This involved measuring the nanoparticles' capacity to adsorb Cr ions from wastewater samples by comparing chromium levels before and after treatment. Removal efficiency for Cr was estimated through the batches such as optimization of pH, contact time, initial Cr concentration and sorbent dose of ZnO NPs were of the batches. These synthesized ZnO NPs were found to be successful in lowering chromium levels in wastewater to meet permissible limit. The nanoparticles exhibited their highest absorption capacity, reaching 94 % (46 mg/g) at pH 4, with a contact time of 7 hours with the optimum sorbent dose of 0.6 g/L. Hence, the excellent adsorption capabilities of these nanoparticles, together with their environmentally benign manufacturing technique, provide a long-term and efficient solution for chromium-contaminated wastewater treatment. Its novel nature has the potential to significantly improve the safety and cleanliness of water ecosystems, protecting the both i.e. human health and the environment.
    Matched MeSH terms: Plant Leaves/chemistry; Nanoparticles/chemistry; Metal Nanoparticles/chemistry
  11. Fulltext Compositional variation in sugars and organic acids at different maturity stages in selected small fruits from pakistan
    Mahmood T, Anwar F, Abbas M, Boyce MC, Saari N
    Int J Mol Sci, 2012;13(2):1380-1392.
    PMID: 22408396 DOI: 10.3390/ijms13021380
    Selected soluble sugars and organic acids were analyzed in strawberry, sweet cherry, and mulberry fruits at different ripening stages by HPLC. The amounts of fructose, glucose and sucrose were found to be: strawberry (1.79-2.86, 1.79-2.25 and 0.01-0.25 g/100 g FW), sweet cherry (0.76-2.35, 0.22-3.39 and 0.03-0.13 g/100 g) and mulberry (3.07-9.41, 1.53-4.95 and 0.01-0.25 g/100 g) at un-ripened to fully-ripened stages, respectively. The strawberry, sweet cherry and mulberry mainly contained tartaric, citric and ascorbic acids in the range of 16-55, 70-1934 and 11-132 mg/100 g; 2-8, 2-10 and 10-17 mg/100 g; 2-118, 139-987 and 2-305 mg/100 g at un-ripened to fully-ripened stages, respectively. Fructose and glucose were established to be the major sugars in all the tested fruit while citric and ascorbic acid were the predominant organic acids in strawberry and mulberry while tartaric acid was mainly present in sweet cherry. The tested fruits mostly showed an increase in the concentration of sugars and organic acids with ripening.
    Matched MeSH terms: Fruit/chemistry*; Prunus/chemistry*; Morus/chemistry*
  12. Nutritional Value, Therapeutic Effects, Phytochemistry, and Toxicology of Lepisanthes fruticosa: A Review
    Siang LJ, Rajak H, Ravichandran V
    Curr Top Med Chem, 2024;24(15):1279-1290.
    PMID: 38639276 DOI: 10.2174/0115680266300963240408051156
    The multifaceted benefits of Lepisanthes fruticosa position it is not only as a promising agricultural commodity but also as a versatile resource with implications for health, biodiversity, and economic growth. Lepisanthes fruticosa has a rich history of traditional use for treating various ailments such as fever and diarrhea. Beyond its traditional uses, the plant's antioxidant properties suggest potential applications in combating oxidative stress-related conditions. Its antihyperglycemic properties indicate promise in managing elevated blood sugar levels, while its antibacterial and antiviral attributes hint at potential applications in infectious disease control. Furthermore, the plant's anticancer properties add to its appeal as a valuable resource in the realm of medical research. The plant also exhibits considerable potential in addressing a range of health concerns, including non-communicable diseases and infections, antidiarrheal, and antiviral properties. In essence, Lepisanthes fruticose emerges as more than just an agricultural asset. Its unique combination of nutritional richness, health benefits, and economic viability underscores its potential to become a valuable asset both locally and on the global stage. In this current review, we are discussed about the ethnopharmacology, nutritional value, therapeutic effects, phytochemistry, and toxicology of Lepisanthes fruticose.
    Matched MeSH terms: Antioxidants/chemistry; Hypoglycemic Agents/chemistry; Plant Extracts/chemistry
  13. Fulltext Three-Component Access to Functionalized Spiropyrrolidine Heterocyclic Scaffolds and Their Cholinesterase Inhibitory Activity
    Boudriga S, Haddad S, Murugaiyah V, Askri M, Knorr M, Strohmann C, et al.
    Molecules, 2020 Apr 23;25(8).
    PMID: 32340203 DOI: 10.3390/molecules25081963
    A novel one-pot [3+2]-cycloaddition reaction of (E)-3-arylidene-1-phenyl-succinimides, cyclic 1,2-diketones (isatin, 5-chloro-isatin and acenaphtenequinone), and diverse α-aminoacids such as 2-phenylglycine or sarcosine is reported. The reaction provides succinimide-substituted dispiropyrrolidine derivatives with high regio- and diastereoselectivities under mild reaction conditions. The stereochemistry of these N-heterocycles has been confirmed by four X-ray diffraction studies. Several synthetized compounds show higher inhibition on acetylcholinesterase (AChE) than butyrylcholinesterase (BChE). Of the 17 synthesized compounds tested, five exhibit good AChE inhibition with IC50 of 11.42 to 22.21 µM. A molecular docking study has also been undertaken for compound 4n possessing the most potent AChE inhibitory activity, disclosing its binding to the peripheral anionic site of AChE enzymes.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry*; Pyrrolidines/chemistry*; Spiro Compounds/chemistry*
  14. Fulltext Neuroprotective Potential of Chrysin: Mechanistic Insights and Therapeutic Potential for Neurological Disorders
    Mishra A, Mishra PS, Bandopadhyay R, Khurana N, Angelopoulou E, Paudel YN, et al.
    Molecules, 2021 Oct 26;26(21).
    PMID: 34770864 DOI: 10.3390/molecules26216456
    Chrysin, a herbal bioactive molecule, exerts a plethora of pharmacological effects, including anti-oxidant, anti-inflammatory, neuroprotective, and anti-cancer. A growing body of evidence has highlighted the emerging role of chrysin in a variety of neurological disorders, including Alzheimer's and Parkinson's disease, epilepsy, multiple sclerosis, ischemic stroke, traumatic brain injury, and brain tumors. Based on the results of recent pre-clinical studies and evidence from studies in humans, this review is focused on the molecular mechanisms underlying the neuroprotective effects of chrysin in different neurological diseases. In addition, the potential challenges, and opportunities of chrysin's inclusion in the neurotherapeutics repertoire are critically discussed.
    Matched MeSH terms: Antineoplastic Agents/chemistry; Flavonoids/chemistry; Neuroprotective Agents/chemistry
  15. Immunoinformatic approach for multi-epitope vaccine design against Staphylococcus aureus based on hemolysin proteins
    Garrido-Palazuelos LI, Almanza-Orduño AA, Waseem M, Basheer A, Medrano-Félix JA, Mukthar M, et al.
    J Mol Graph Model, 2024 Nov;132:108848.
    PMID: 39182254 DOI: 10.1016/j.jmgm.2024.108848
    Staphylococcus aureus is a common bacterium that causes a variety of infections in humans. This microorganism produces several virulence factors, including hemolysins, which contribute to its disease-causing ability. The treatment of S. aureus infections typically involves the use of antibiotics. However, the emergence of antibiotic-resistant strains has become a major concern. Therefore, vaccination against S. aureus has gained attention as an alternative approach. Vaccination has the advantage of stimulating the immune system to produce specific antibodies that can neutralize bacteria and prevent infection. However, developing an effective vaccine against S. aureus has proven to be challenging. This study aimed to use in silico methods to design a multi-epitope vaccine against S. aureus infection based on hemolysin proteins. The designed vaccine contained four B-cell epitopes, four CTL epitopes, and four HTL epitopes, as well as the ribosomal protein L7/L12 and pan-HLA DR-binding epitope, included as adjuvants. Furthermore, the vaccine was non-allergenic and non-toxic with the potential to stimulate the TLR2-, TLR-4, and TLR-6 receptors. The predicted vaccine exhibited a high degree of antigenicity and stability, suggesting potential for further development as a viable vaccine candidate. The population coverage of the vaccine was 94.4 %, indicating potential widespread protection against S. aureus. Overall, these findings provide valuable insights into the design of an effective multi-epitope vaccine against S. aureus infection and pave the way for future experimental validations.
    Matched MeSH terms: Epitopes/chemistry; Staphylococcal Vaccines/chemistry; Epitopes, T-Lymphocyte/chemistry
  16. Fulltext Plant carbonic anhydrase-like enzymes in neuroactive alkaloid biosynthesis
    Nett RS, Dho Y, Tsai C, Passow D, Martinez Grundman J, Low YY, et al.
    Nature, 2023 Dec;624(7990):182-191.
    PMID: 37938780 DOI: 10.1038/s41586-023-06716-y
    Plants synthesize numerous alkaloids that mimic animal neurotransmitters1. The diversity of alkaloid structures is achieved through the generation and tailoring of unique carbon scaffolds2,3, yet many neuroactive alkaloids belong to a scaffold class for which no biosynthetic route or enzyme catalyst is known. By studying highly coordinated, tissue-specific gene expression in plants that produce neuroactive Lycopodium alkaloids4, we identified an unexpected enzyme class for alkaloid biosynthesis: neofunctionalized α-carbonic anhydrases (CAHs). We show that three CAH-like (CAL) proteins are required in the biosynthetic route to a key precursor of the Lycopodium alkaloids by catalysing a stereospecific Mannich-like condensation and subsequent bicyclic scaffold generation. Also, we describe a series of scaffold tailoring steps that generate the optimized acetylcholinesterase inhibition activity of huperzine A5. Our findings suggest a broader involvement of CAH-like enzymes in specialized metabolism and demonstrate how successive scaffold tailoring can drive potency against a neurological protein target.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry; Sesquiterpenes/chemistry; Lycopodium/chemistry
  17. Designing potential lead compounds targeting aminoglycoside N (6')-acetyltransferase in Serratia marcescens: A drug discovery strategy
    Prabhu D, Shankari G, Rajamanikandan S, Jeyakanthan J, Velusamy P, Gopinath SCB, et al.
    Int J Biol Macromol, 2024 Nov;281(Pt 1):136976.
    PMID: 39490491 DOI: 10.1016/j.ijbiomac.2024.136976
    Serratia marcescens is an opportunistic human pathogen that causes urinary tract infections, ocular lens infections, and respiratory tract infections. S. marcescens employs various defense mechanisms to evade antibiotics, one of which is mediated by aminoglycoside N-acetyltransferase (AAC). In this mechanism, the enzyme AAC facilitates the transfer and linkage of the acetyl moiety from the donor substrate acetyl-coenzyme A to specific positions on antibiotics. This modification alters the antibiotic's structure, leading to the inactivation of aminoglycoside antibiotics. In the current scenario, antibiotic resistance has become a global threat, and targeting the enzymes that mediate resistance is considered crucial to combat this issue. The study aimed to address the increasing global threat of antibiotic resistance in Serratia marcescens by targeting the aminoglycoside N-acetyltransferase (AAC (6')) enzyme, which inactivates aminoglycoside antibiotics through acetylation. Due to the absence of experimental structure, we constructed a homology model of aminoglycoside N (6')-acetyltransferase (AAC (6')) of S. marcescens using the atomic structure of aminoglycoside N-acetyltransferase AAC (6')-Ib (PDB ID: 1V0C) as a template. The stable architecture and integrity of the modelled AAC (6') structure were analyzed through a 100 ns simulation. Structure-guided high-throughput screening of four small molecule databases (Binding, Life Chemicals, Zinc, and Toslab) resulted in the identification of potent inhibitors against AAC (6'). The hits obtained from screening were manually clustered, and the five hit molecules were shortlisted based on the docking score, which are observed in the range of -17.09 kcal/mol to -11.95 kcal/mol. These selected five molecules displayed acceptable pharmacological properties in ADME predictions. The binding free energy calculations, and molecular dynamics simulations of ligand bound AAC (6') complexes represented higher affinity and stable binding. The selected molecules demonstrated stable binding with AAC (6'), indicating their strong potential to hamper the binding of aminoglycoside in the respective site. and thereby inhibit. This process mitigates enzyme mediated AAC (6') activity on aminoglycosides and reverse the bactericidal function of aminoglycosides, and also this method could serve as a platform for the development of potential antimicrobials.
    Matched MeSH terms: Aminoglycosides/chemistry; Anti-Bacterial Agents/chemistry; Enzyme Inhibitors/chemistry
  18. Fulltext Antioxidant Activities of 4-Methylumbelliferone Derivatives
    Al-Majedy YK, Al-Amiery AA, Kadhum AA, Mohamad AB
    PLoS One, 2016;11(5):e0156625.
    PMID: 27243231 DOI: 10.1371/journal.pone.0156625
    The synthesis of derivatives of 4-Methylumbelliferone (4-MUs), which are structurally interesting antioxidants, was performed in this study. The modification of 4-Methylumbelliferone (4-MU) by different reaction steps was performed to yield the target compounds, the 4-MUs. The 4-MUs were characterized by different spectroscopic techniques (Fourier transform infrared; FT-IR and Nuclear magnetic resonance; NMR) and micro-elemental analysis (CHNS). The in vitro antioxidant activity of the 4-MUs was evaluated in terms of their free radical scavenging activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH), Nitric oxide radical scavenging activity assay, chelating activity and their (FRAP) ferric-reducing antioxidant power, which were compared with a standard antioxidant. Our results reveal that the 4-MUs exhibit excellent radical scavenging activities. The antioxidant mechanisms of the 4-MUs were also studied. Density Function Theory (DFT)-based quantum chemical studies were performed with the basis set at 3-21G. Molecular models of the synthesized compounds were studied to understand the antioxidant activity. The electron levels, namely HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital), for these synthesized antioxidants were also studied.
    Matched MeSH terms: Biphenyl Compounds/chemistry*; Hydrogen Peroxide/chemistry; Nitric Oxide/chemistry; Picrates/chemistry*; Triazines/chemistry*; Free Radical Scavengers/chemistry*
  19. Horseradish peroxidase-labeled silver/reduced graphene oxide thin film-modified screen-printed electrode for detection of carcinoembryonic antigen
    Lee SX, Lim HN, Ibrahim I, Jamil A, Pandikumar A, Huang NM
    Biosens Bioelectron, 2017 Mar 15;89(Pt 1):673-680.
    PMID: 26718548 DOI: 10.1016/j.bios.2015.12.030
    In this study, a disposable and simple electrochemical immunosensor was fabricated for the detection of carcinoembryonic antigen. In this method, silver nanoparticles (AgNPs) were mixed with reduced graphene oxide (rGO) to modify the surface of screen-printed carbon electrode (SPE). Initially, AgNPs-rGO modified-SPEs were fabricated by using simple electrochemical deposition method. Then the carcinoembryonic antigen (CEA) was immobilized between the primary antibody and horseradish peroxidase (HRP)-conjugated secondary antibody onto AgNPs-rGO modified-SPEs to fabricate a sandwich-type electrochemical immunosensor. The proposed method could detect the CEA with a linear range of 0.05-0.50µgmL-1 and a detection limit down to 0.035µgmL-1 as compared to its non-sandwich counterpart, which yielded a linear range of 0.05-0.40µgmL-1, with a detection limit of 0.042µgmL-1. The immunosensor showed good performance in the detection of carcinoembryonic antigen, exhibiting a simple, rapid and low-cost. The immunosensor showed a higher sensitivity than an enzymeless sensor.
    Matched MeSH terms: Graphite/chemistry*; Horseradish Peroxidase/chemistry; Oxides/chemistry; Silver/chemistry*; Metal Nanoparticles/chemistry*; Antibodies, Immobilized/chemistry
  20. Fulltext Long-term xeno-free culture of human pluripotent stem cells on hydrogels with optimal elasticity
    Higuchi A, Kao SH, Ling QD, Chen YM, Li HF, Alarfaj AA, et al.
    Sci Rep, 2015 Dec 14;5:18136.
    PMID: 26656754 DOI: 10.1038/srep18136
    The tentative clinical application of human pluripotent stem cells (hPSCs), such as human embryonic stem cells and human induced pluripotent stem cells, is restricted by the possibility of xenogenic contamination resulting from the use of mouse embryonic fibroblasts (MEFs) as a feeder layer. Therefore, we investigated hPSC cultures on biomaterials with different elasticities that were grafted with different nanosegments. We prepared dishes coated with polyvinylalcohol-co-itaconic acid hydrogels grafted with an oligopeptide derived from vitronectin (KGGPQVTRGDVFTMP) with elasticities ranging from 10.3 to 30.4 kPa storage moduli by controlling the crosslinking time. The hPSCs cultured on the stiffest substrates (30.4 kPa) tended to differentiate after five days of culture, whereas the hPSCs cultured on the optimal elastic substrates (25 kPa) maintained their pluripotency for over 20 passages under xeno-free conditions. These results indicate that cell culture matrices with optimal elasticity can maintain the pluripotency of hPSCs in culture.
    Matched MeSH terms: Culture Media/chemistry; Immunohistochemistry; Polyvinyl Alcohol/chemistry; Succinates/chemistry; Xenobiotics/chemistry; Vitronectin/chemistry; Hydrogels/chemistry*
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