Displaying publications 1 - 20 of 161 in total

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  1. Siddiqui R, Khodja A, Ibrahim T, Khamis M, Anwar A, Khan NA
    World J Microbiol Biotechnol, 2023 Oct 04;39(12):330.
    PMID: 37792153 DOI: 10.1007/s11274-023-03760-8
    With the rise of antibiotic resistance globally, coupled with evolving and emerging infectious diseases, there is an urgent need for the development of novel antimicrobials. Deep eutectic solvents (DES) are a new generation of eutectic mixtures that depict promising attributes with several biological implications. DES exhibit unique properties such as low toxicity, biodegradability, and high thermal stability. Herein, the antimicrobial properties of DES and their mechanisms of action against a range of microorganisms, including bacteria, amoebae, fungi, viruses, and anti-cancer properties are reviewed. Overall, DES represent a promising class of novel antimicrobial agents as well as possessing other important biological attributes, however, future studies on DES are needed to investigate their underlying antimicrobial mechanism, as well as their in vivo effects, for use in the clinic and public at large.
  2. Majeed Butt O, Shakeel Ahmad M, Kai Lun T, Seng Che H, Fayaz H, Abd Rahim N, et al.
    Waste Manag, 2023 Feb 01;156:1-11.
    PMID: 36424243 DOI: 10.1016/j.wasman.2022.11.016
    The integration of hydrogen in the primary energy mix requires a major technological shift in virtually every energy-related application. This study has attempted to investigate the techno-economic solar photovoltaic (PV) integrated water electrolysis and waste incineration system. Three different strategies, i.e., (i) PV + Battery(Hybrid mode with required batteries); (ii) auto-ignition (Direct coupling); and (iii) PV + Secondary-Electrolyzer(Direct coupling assisted with secondary electrolyzer), have been envisioned. The 'PV + Battery' consume 42.42 % and 15.07 % less energy than the auto-ignition and 'PV + Secondary-Electrolyzer' methods. However, the capital cost of 'PV + Battery' has been calculated to be 15.4 % and 11.8 % more than auto-ignition and 'PV + Secondary-Electrolyzer, respectively.The energy consumption relative to waste input, the 'PV + Battery' method used 80 % less energy, while auto-ignition and 'PV + Secondary-Electrolyzer' showed 70.5 % and 77.5 % less energy, respectively. Furthermore, these approaches showed a vast difference in cost-benefit for the longer run. 'PV + Battery' was forecasted to be 73.3 % and 23.3 % more expensive than auto-ignition and 'PV + Secondary-Electrolyzer' methods, respectively, for 30 years. Overall, this study can benefit from using either of these methods depending on the application, usage scale, and climatic conditions.
  3. Lee SW, Liong ML, Yuen KH, Leong WS, Cheah PY, Khan NA, et al.
    Urology, 2008 Jan;71(1):79-84.
    PMID: 18242370 DOI: 10.1016/j.urology.2007.08.043
    OBJECTIVES: To examine the prevalence, characteristics, and impact of sexual dysfunction in our primary care referral population.
    METHODS: Participants seeking treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) were recruited from general urology clinics. The subjects completed the National Institutes of Health-Chronic Prostatitis Symptom Index, International Index of Erectile Function-5, and selected questions from the University of Washington Symptom Score. Additional information on demographics and medical and treatment history were also obtained. Sexual dysfunction was defined as self-reported erectile dysfunction (ED) or ejaculatory difficulty, or both.
    RESULTS: Of 296 participants with CP/CPPS, 214 (72.3%) reported sexual dysfunction. The National Institutes of Health-Chronic Prostatitis Symptom Index total score averaged 22.5 +/- 6.9 for participants with sexual dysfunction compared with 20.4 +/- 7.8 for participants who did not report sexual dysfunction (P = 0.03). Of the 214 participants with sexual dysfunction, 54 (25.0%) complained of ED only, 71 (33.4%) complained of ejaculatory difficulties only, and 89 (41.6%) complained of both ED and ejaculatory difficulties. Men reporting both ED and ejaculatory difficulty reported worse CP/CPPS symptoms (analysis of variance, P = 0.042) and worse quality of life (analysis of variance, P = 0.006) than men without sexual dysfunction.
    CONCLUSIONS: Sexual dysfunction was reported by almost three quarters of patients with CP/CPPS. Patients with CP/CPPS and sexual dysfunction experienced substantially worse symptoms, particularly worse quality of life, than other patients with CP/CPPS. Sexual dysfunction merits consideration as an important aspect of CP/CPPS and a potential outcome measure.

    Study site: general urology clinics
    in Penang
  4. Lim R, Liong ML, Leong WS, Khan NA, Yuen KH
    Trials, 2015;16:279.
    PMID: 26093910 DOI: 10.1186/s13063-015-0803-1
    There is currently a lack of randomized, sham-controlled trials that are adequately powered, using validated outcomes, to allow for firm recommendations on the use of magnetic stimulation for stress urinary incontinence. We report a protocol of a multicenter, randomized, double-blind, sham-controlled parallel-group trial to evaluate the efficacy of magnetic stimulation for stress urinary incontinence.
  5. Loh LN, McCarthy EMC, Narang P, Khan NA, Ward TH
    Traffic, 2017 11;18(11):733-746.
    PMID: 28799243 DOI: 10.1111/tra.12508
    Eukaryotic cells utilize multiple endocytic pathways for specific uptake of ligands or molecules, and these pathways are commonly hijacked by pathogens to enable host cell invasion. Escherichia coli K1, a pathogenic bacterium that causes neonatal meningitis, invades the endothelium of the blood-brain barrier, but the entry route remains unclear. Here, we demonstrate that the bacteria trigger an actin-mediated uptake route, stimulating fluid phase uptake, membrane ruffling and macropinocytosis. The route of uptake requires intact lipid rafts as shown by cholesterol depletion. Using a variety of perturbants we demonstrate that small Rho GTPases and their downstream effectors have a significant effect on bacterial invasion. Furthermore, clathrin-mediated endocytosis appears to play an indirect role in E. coli K1 uptake. The data suggest that the bacteria effect a complex interplay between the Rho GTPases to increase their chances of uptake by macropinocytosis into human brain microvascular endothelial cells.
  6. Siddiqui R, Yee Ong TY, Maciver S, Khan NA
    Ther Deliv, 2023 Aug;14(8):485-490.
    PMID: 37691579 DOI: 10.4155/tde-2023-0032
    Aim: CNS infections due to parasites often prove fatal. In part, this is due to inefficacy of drugs to cross the blood-brain barrier. Methods: Here, we tested intranasal and intravenous route and compared adverse effects of Amphotericin B administration, through blood biochemistry, liver, kidney and brain histopathological evidence of toxicities in vivo post-administration. Results: It was observed that intranasal route limits the adverse side effects of Amphotericin B, in contrast to intravenous route. Conclusion: As parasites such as Naegleria fowleri exhibit unequivocal affinity toward the olfactory bulb and frontal lobe in the central nervous system, intranasal administration would directly reach amoebae bypassing the blood-brain barrier selectivity and achieve the minimum inhibitory concentration at the target site.
  7. Magosso E, Ansari MA, Gopalan Y, Abu Bakar MR, Karim Khan NA, Wong JW, et al.
    PMID: 21073069
    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and a frequent finding on ultrasound examination. NAFLD is considered as the liver component of metabolic syndrome and is linked to accelerated atherosclerosis and cardiovascular disease. No data from systematic studies regarding the prevalence of NAFLD are available for the Malaysian population. One hundred eighty untreated hypercholesterolemic volunteers underwent blood and ultrasound examinations to evaluate their livers. NAFLD was diagnosed in 102 subjects (56.7%) with similar prevalences between sexes. Of the 102 positive subjects 82 (80.4%) were graded as mild, 17 (16.7%) as moderate and 3 (2.9%) as severe fatty liver cases. Elevated fasting plasma glucose (FPG) levels were found in 13 of 180 subjects (7.2%), while elevated AST and ALT levels were seen in 30 (16.7%) and 22 (12.2%) of the180 subjects, respectively.
  8. Khan AH, Aziz HA, Khan NA, Dhingra A, Ahmed S, Naushad M
    Sci Total Environ, 2021 Nov 10;794:148484.
    PMID: 34217082 DOI: 10.1016/j.scitotenv.2021.148484
    The occurrence of pharmaceutical residues in the aquatic ecosystem is an emerging concern of environmentalists. This study primarily investigated the seasonal variation of high-priority pharmaceutical residues in the Yamuna River, accompanied by 22 drains discharge from different parts of Delhi. Five sampling sites were selected for analyzing high-priority pharmaceuticals along with physico-chemical and biological parameters for 3 season's viz. pre-monsoon (PrM), monsoon (DuM), and post-monsoon (PoM), respectively. The maximum occurrences were detected during the PoM, compared to the PrM and DuM seasons. The maximum concentration of BOD, COD, and Phosphate was detected at the last sampling station (SP-5). Similarly, all targeted pharmaceuticals concentration were maximum at the last sampling point i.e. Okhla barrage (SP-5, max: DIC = 556.1 ng/l, IBU = 223.4 ng/l, CAR = 183.1 ng/l, DIA = 457.8 ng/l, OFL = 1726.5 ng/l, FRU = 312.2 ng/l and SIM = 414.9 ng/l) except at Barapulla downstream (SP-4, max: ERY = 178.1 ng/l). The mean concentrations of Fecal coliform (FC) ranged from 1700 to 6500 CFU/100 ml. The maximum colonies were detected in PrM season (6500 CFU/100 ml) followed by PoM (5800 CFU/100 ml) and least in DuM (1700 CFU/100 ml). Risk quotient (RQ) analysis of high-priority pharmaceuticals indicated high ecotoxicological risks exposure (>1) from DIC, DIA, OFL, and SIM in all seasons at all the sampling sites. However, lower risk was predicted for IBU, CAR, ERY, and FRU, respectively. This risk assessment indicated an aquatic ecosystem potentially exposed to high risks from these pharmaceutical residues. Moreover, seasonal agricultural application, rainfall, and temperature could influence the levels and compositions of pharmaceutical residue in the aquatic ecosystem. Hence, attention is required particularly to this stream since it is only a local lifeline source for urban consumers for domestic water supply and farmers for cultivation.
  9. Low BY, Liong ML, Yuen KH, Chee C, Leong WS, Chong WL, et al.
    J Urol, 2008 Apr;179(4):1461-9.
    PMID: 18295277 DOI: 10.1016/j.juro.2007.11.060
    PURPOSE: We determined the clinical efficacy and safety of terazosin in the treatment of patients with female lower urinary tract symptoms.
    MATERIALS AND METHODS: A total of 100 females 20 to 70 years old who met the inclusion criteria of total International Prostate Symptom Score 8 or greater, symptom duration 1 or more months, and did not meet any exclusion criteria were entered into the study. Subjects were randomized to receive terazosin or placebo in titrated dose from 1 mg od, 1 mg twice daily to 2 mg twice daily during 14 weeks. Successful treatment outcomes use primary end point of International Prostate Symptom Score quality of life 2 or less and secondary end point of total International Prostate Symptom Score 7 or less. Other outcome measures included International Prostate Symptom Score individual item scores, King's Health Questionnaire quality of life domains, objective assessment parameters of 24-hour frequency volume chart, maximum flow rate and post-void residual urine.
    RESULTS: Using a primary end point, 32 of 40 (80%) evaluable terazosin subjects responded in contrast to 22 of 40 (55%) evaluable placebo subjects (p <0.02). The secondary end point revealed a successful outcome in 85% of terazosin subjects vs 55% in placebo (p <0.01). Of the 7 International Prostate Symptom Score individual item scores, only item scores of frequency and straining showed statistically significant reductions with terazosin (p <0.01). All King's Health Questionnaire quality of life domains except domain of severity measures showed statistically significant improvement with terazosin (p <0.05). There were no differences between treatment groups in all objective assessment parameters. Of all evaluable subjects 23 of 40 (58%) on placebo experienced adverse events vs 16 of 40 (40%) on terazosin (p >0.05).
    CONCLUSIONS: Terazosin proved to be more effective and safe than placebo in patients with female lower urinary tract symptoms.
  10. Lim R, Liong ML, Leong WS, Khan NA, Yuen KH
    J Urol, 2016 07;196(1):153-8.
    PMID: 26812304 DOI: 10.1016/j.juro.2016.01.090
    PURPOSE: Studies of the effects of stress urinary incontinence on the sexual function of couples are scarce. We prospectively evaluated couple sexual function and the relationship between sexual function and quality of life. We also compared quality of life in females with vs without stress urinary incontinence.

    MATERIALS AND METHODS: Sexually active females at least 21 years old with or without stress urinary incontinence and their partners were recruited for study. To assess sexual function the couples completed GRISS (Golombok Rust Inventory of Sexual Satisfaction) and a 1-item question on overall sexual experience, "Over the past 4 weeks, how satisfied have you been with your overall sexual life?" Additionally, females completed ICIQ-LUTSqol (International Consultation on Incontinence Questionnaire-Lower Urinary Tract Symptoms Quality of Life) to assess quality of life.

    RESULTS: For sexual function assessment 66 of 134 couples with (49.3%) and 95 of 176 without (54.0%) stress urinary incontinence were recruited. Females with stress urinary incontinence had lower overall sexual function, lower frequency of sexual intercourse, less satisfaction (each p <0.001) and higher avoidance behavior (p = 0.026). Partners of females with stress urinary incontinence had more problems with erectile dysfunction (p = 0.027), less satisfaction (p = 0.006) and lower frequency of sexual intercourse (p = 0.001) but no difference in overall GRISS score (p = 0.093). Couples with stress urinary incontinence had poorer overall sexual experience (p <0.05). Females with stress urinary incontinence had poorer quality of life than those without stress urinary incontinence (120 of 134, response rate 89.6% vs 145 of 176, response rate 82.4%, p <0.001). Sexual function and quality of life did not significantly correlate (r = 0.001, p = 0.997).

    CONCLUSIONS: Stress urinary incontinence in females is negatively associated not only with female quality of life and sexual function but also with partner sexual function.

  11. Lim R, Liong ML, Leong WS, Karim Khan NA, Yuen KH
    J Urol, 2017 05;197(5):1302-1308.
    PMID: 27871927 DOI: 10.1016/j.juro.2016.11.091
    PURPOSE: Despite significant differences in success rates between surgical and nonsurgical treatments for female stress urinary incontinence, a few cross-sectional surveys showed that most patients still prefer the latter. We evaluated the efficacy of the under studied nonsurgical treatment using pulsed magnetic stimulation for female stress urinary incontinence.

    MATERIALS AND METHODS: This randomized, double-blind, sham controlled study was performed in 120 female subjects at least 21 years old with stress urinary incontinence. Treatment involved pulsed magnetic stimulation for 2 sessions per week for 2 months (16 sessions). After 2 months, subjects could opt for 16 additional sessions regardless of initial randomization. The primary response criterion was a 5-point reduction in the ICIQ-UI SF (International Consultation on Incontinence Questionnaire for Urinary Incontinence-Short Form) score. Key secondary response criteria included objective and subjective cure, supplemented by other secondary criteria. Followups were performed at months 1, 2, 5, 8 and 14.

    RESULTS: At 2 months 45 of 60 subjects (75%) in the active arm vs 13 of 60 (21.7%) in the sham arm were treatment responders (p <0.001). After 2 months 24 subjects (40%) in the active arm and 41 (68%) in the sham arm elected additional active pulsed magnetic stimulation. At 14 months, subjects who received 32 sessions of active pulsed magnetic stimulation had the highest percentage of treatment responders (18 of 24 or 75.0%), followed by those who received 16 sessions (26 of 36 or 72.2% and 28 of 41 or 68.3%) and those who did not receive any active pulsed magnetic stimulation (4 of 19 or 21.1%) (p <0.001).

    CONCLUSIONS: The encouraging long-term response rates show that pulsed magnetic stimulation is an attractive nonsurgical alternative for patients who do not want to undergo surgery.

  12. Ali SM, Siddiqui R, Khan NA
    J Pharm Pharmacol, 2018 Oct;70(10):1287-1300.
    PMID: 30003546 DOI: 10.1111/jphp.12976
    OBJECTIVES: Whether vertebrates/invertebrates living in polluted environments are an additional source of antimicrobials.

    KEY FINDINGS: Majority of antimicrobials have been discovered from prokaryotes and those which are of eukaryotic origin are derived mainly from fungal and plant sources. With this in mind, it is important to note that pests, such as cockroaches come across pathogenic bacteria routinely, yet thrive in polluted environments. Other animals, such as snakes thrive from feeding on germ-infested rodents. Logically, such species must have developed an approach to protect themselves from these pathogens, yet they have largely been ignored as a potential source of antimicrobials despite their remarkable capability to fight disease-causing organisms.

    SUMMARY: Animals living in polluted environments are an underutilized source for potential antimicrobials, hence it is believed that several novel bioactive molecule(s) will be identified from these sources to counter increasingly resistant bacterial infections. Further research will be necessary in the development of novel antimicrobial(s) from these unusual sources which will have huge clinical impact worldwide.

  13. Walvekar S, Anwar A, Anwar A, Lai NJY, Yow YY, Khalid M, et al.
    J Parasitol, 2021 07 01;107(4):537-546.
    PMID: 34265050 DOI: 10.1645/21-41
    Nanomedicine has the potential in enhancing the efficacy and bioavailability of anti-infective agents. Here we determined whether conjugation of the Malaysian cultivated seaweed Kappaphycus alvarezii with silver-conjugated nanoparticles enhanced anti-acanthamoebic properties. Silver-conjugated K. alvarezii were successfully synthesized, followed by characterization with Fourier transform infrared spectroscopy, ultraviolet-visible spectrophotometry, and transmission electron microscopy. Amoebicidal effects were evaluated against Acanthamoeba castellanii, and cytotoxicity assays were performed using HaCaT cells. Viability assays revealed that silver nanoparticles conjugated with K. alvarezii extract exhibited significant antiamoebic properties (P < 0.05). Nano-conjugates induced the production of reactive oxygen species. Importantly, silver-conjugated extract inhibited amoeba-mediated host cell damage as established by lactate dehydrogenase release. Neither the nano-conjugates nor the extract showed cytotoxicity against human cells in vitro. Liquid chromatography and mass spectroscopy revealed several molecules, including 2,6-nonadien-1-ol, N-desmethyl trifluoperazine, dulciol B, lucidumol A, acetoxolone, 2-[4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl]-5-(octyloxy)phenol, C16 sphinganine, 22-tricosenoic acid, and β-dihydrorotenone, of which dulciol B and C16 sphinganine are known to possess antimicrobial activities. In summary, marine organisms are an important source of bioactive molecules with anti-acanthamoebic properties that can be enhanced by conjugating with silver nanoparticles. Natural products combined with nanotechnology using multifunctional nanoparticle complexes can deliver therapeutic agents effectively and hold promise in the development of new formulations of anti-acanthamoebic agents.
  14. Gopalan Y, Shuaib IL, Magosso E, Ansari MA, Abu Bakar MR, Wong JW, et al.
    Stroke, 2014 May;45(5):1422-8.
    PMID: 24699052 DOI: 10.1161/STROKEAHA.113.004449
    Previous cell-based and animal studies showed mixed tocotrienols are neuroprotective, but the effect is yet to be proven in humans. Thus, the present study aimed to evaluate the protective activity of mixed tocotrienols in humans with white matter lesions (WMLs). WMLs are regarded as manifestations of cerebral small vessel disease, reflecting varying degrees of neurodegeneration and tissue damage with potential as a surrogate end point in clinical trials.
  15. Anwar A, Minhaz A, Hussain SS, Anwar A, Simjee SU, Ishaq M, et al.
    Spectrochim Acta A Mol Biomol Spectrosc, 2019 Jan 05;206:135-140.
    PMID: 30096697 DOI: 10.1016/j.saa.2018.07.099
    Gold nanoparticles (AuNPs) stabilized by new cationic 1‑(3‑(acetylthio)propyl)pyrazin‑1‑ium ligand (PPTA) were synthesized. AuNPs stabilized by PPTA (PPTA-AuNPs) were found to be spherical and polydispersed with the average size of 60 nm. Human neuroblastoma (SHSY-5Y) cells permeability of PPTA-AuNPs was found to be a key feature to study the intracellular quenching of Fe(III) proliferative activity. In vitro MTT assay revealed non-cytotoxicity of PPTA and PPTA-AuNPs at 100 μM concentration, while treatment of 100 μM of Fe(III) with SHSY-5Y cells resulted into higher cells viability. Contrary, a mixture of 1:1 Fe(III) with PPTA-AuNPs showed no change in the viability of cells at same concentration which suggests the intracellular complexation and recognition of Fe(III) by PPTA-AuNPs. AFM morphological analysis of SHSY-5Y cells also supported the MTT assay results, and it is safe to conclude that PPTA-AuNPs can be used as Fe(III) probes in living cells. In addition, Fe(III) caused a significant decrease in the absorbance of surface plasmon resonance (SPR) band of PPTA-AuNPs in a wide range of concentration and pH, with limit of detection 4.3 μM. Moreover, the specific response of PPTA-AuNPs towards Fe(III) was unaffected by the interference of other metals and components of real samples of tap water.
  16. Alkinani MH, Almazroi AA, Jhanjhi NZ, Khan NA
    Sensors (Basel), 2021 Oct 18;21(20).
    PMID: 34696118 DOI: 10.3390/s21206905
    Internet of Things (IoT) and 5G are enabling intelligent transportation systems (ITSs). ITSs promise to improve road safety in smart cities. Therefore, ITSs are gaining earnest devotion in the industry as well as in academics. Due to the rapid increase in population, vehicle numbers are increasing, resulting in a large number of road accidents. The majority of the time, casualties are not appropriately discovered and reported to hospitals and relatives. This lack of rapid care and first aid might result in life loss in a matter of minutes. To address all of these challenges, an intelligent system is necessary. Although several information communication technologies (ICT)-based solutions for accident detection and rescue operations have been proposed, these solutions are not compatible with all vehicles and are also costly. Therefore, we proposed a reporting and accident detection system (RAD) for a smart city that is compatible with any vehicle and less expensive. Our strategy aims to improve the transportation system at a low cost. In this context, we developed an android application that collects data related to sound, gravitational force, pressure, speed, and location of the accident from the smartphone. The value of speed helps to improve the accident detection accuracy. The collected information is further processed for accident identification. Additionally, a navigation system is designed to inform the relatives, police station, and the nearest hospital. The hospital dispatches UAV (i.e., drone with first aid box) and ambulance to the accident spot. The actual dataset from the Road Safety Open Repository is used for results generation through simulation. The proposed scheme shows promising results in terms of accuracy and response time as compared to existing techniques.
  17. Akbar N, Khan NA, Sagathevan K, Iqbal M, Tawab A, Siddiqui R
    Sci Rep, 2019 11 18;9(1):17012.
    PMID: 31740685 DOI: 10.1038/s41598-019-52738-w
    Antimicrobial resistance is a major threat to human health, hence there is an urgent need to discover antibacterial molecule(s). Previously, we hypothesized that microbial gut flora of animals are a potential source of antibacterial molecules. Among various animals, Cuora amboinensis (turtle) represents an important reptile species living in diverse ecological environments and feed on organic waste and terrestrial organisms and have been used in folk medicine. The purpose of this study was to mine turtle's gut bacteria for potential antibacterial molecule(s). Several bacteria were isolated from the turtle gut and their conditioned media were prepared. Conditioned media showed potent antibacterial activity against several Gram-positive (Bacillus cereus, Streptococcus pyogenes and methicillin-resistant Staphylococcus aureus) and Gram-negative (neuropathogenic Escherichia coli K1, Serratia marcescens, Pseudomonas aeruginosa, Salmonella enterica and Klebsiella pneumoniae) pathogenic bacteria. Conditioned media-mediated bactericidal activity was heat-resistant when treated at 95°C for 10 min. By measuring Lactate dehydrogenase release, the results showed that conditioned media had no effect on human cell viability. Tandem Mass Spectrometric analysis revealed the presence of various secondary metabolites, i.e., a series of known as well as novel N-acyl-homoserine lactones, several homologues of 4-hydroxy-2-alkylquinolines, and rhamnolipids, which are the signature metabolites of Pseudomonas species. These findings are significant and provide the basis for rational development of therapeutic interventions against bacterial infections.
  18. Anwar A, Masri A, Rao K, Rajendran K, Khan NA, Shah MR, et al.
    Sci Rep, 2019 02 28;9(1):3122.
    PMID: 30816269 DOI: 10.1038/s41598-019-39528-0
    Herein, we report green synthesized nanoparticles based on stabilization by plant gums, loaded with citrus fruits flavonoids Hesperidin (HDN) and Naringin (NRG) as novel antimicrobial agents against brain-eating amoebae and multi-drug resistant bacteria. Nanoparticles were thoroughly characterized by using zetasizer, zeta potential, atomic force microscopy, ultravoilet-visible and Fourier transform-infrared spectroscopic techniques. The size of these spherical nanoparticles was found to be in the range of 100-225 nm. The antiamoebic effects of these green synthesized Silver and Gold nanoparticles loaded with HDN and NRG were tested against Acanthamoeba castellanii and Naegleria fowleri, while antibacterial effects were evaluated against methicillin-resistant Staphylococcus aureus (MRSA) and neuropathogenic Escherichia coli K1. Amoebicidal assays revealed that HDN loaded Silver nanoparticles stabilized by gum acacia (GA-AgNPs-HDN) quantitatively abolished amoeba viability by 100%, while NRG loaded Gold nanoparticles stabilized by gum tragacanth (GT-AuNPs-NRG) significantly reduced the viability of A. castellanii and N. fowleri at 50 µg per mL. Furthermore, these nanoparticles inhibited the encystation and excystation by more than 85%, as well as GA-AgNPs-HDN only completely obliterated amoeba-mediated host cells cytopathogenicity. Whereas, GA-AgNPs-HDN exhibited significant bactericidal effects against MRSA and E. coli K1 and reduced bacterial-mediated host cells cytotoxicity. Notably, when tested against human cells, these nanoparticles showed minimal (23%) cytotoxicity at even higher concentration of 100 µg per mL as compared to 50 µg per mL used for antimicrobial assays. Hence, these novel nanoparticles formulations hold potential as therapeutic agents against infections caused by brain-eating amoebae, as well as multi-drug resistant bacteria, and recommend a step forward in drug development.
  19. Mohd Hussain RH, Afiqah WN, Abdul Ghani MK, Khan NA, Siddiqui R, Anuar TS
    Saudi J Biol Sci, 2021 Apr;28(4):2352-2359.
    PMID: 33911949 DOI: 10.1016/j.sjbs.2021.01.030
    The incidence of Acanthamoeba keratitis has been increasing since the previous decades, especially among contact lens users. This infection is majorly caused by the use of ineffective contact lens disinfecting solution. Thus, this study was conducted to evaluate the in vitro effects of multi-purpose disinfecting solutions (MPDS) against Acanthamoeba trophozoites and cysts. Acanthamoeba genotype T4 isolated from contact lens paraphernalia and an environmental strains were propagated for trophozoite or cyst-containing culture and adjusted in final concentration of 1 × 105 cells/ml. Amoebicidal and cysticidal assays were conducted by incubating trophozoites and cysts with OPTI-FREE® Express®, ReNu® Fresh™, Complete® Multi-Purpose Solution and AVIZOR Unica® Sensitive according to the manufacturer's minimum recommended disinfectant time (MMRDT) for up to 12 h at 30 ⁰C. Trypan blue hemocytometer-based microscopic counts determined amoebicidal and cysticidal effects. The viability of Acanthamoeba trophozoites and cysts was confirmed by re-inoculated them in the 1.5% non-nutrient agar plates. It was found that none of the MPDS showed amoebicidal and cysticidal effects during the MMRDT. However, OPTI-FREE® Express® demonstrated a significant differences in average cell reduction for both stages within MMRDT. When subjected to 12 h exposure, both OPTI-FREE® Express® and ReNu® Fresh™ led to significant reduction in the number of trophozoite and cyst cells. Notably, Complete® Multi-Purpose Solution and AVIZOR Unica® Sensitive did appreciably improve the solution effectiveness towards trophozoite cells when incubated for 12 h. All MPDS were largely ineffective, with 100% survival of all isolates at MMRDT, while OPTI-FREE® Express® showed limited amoebicidal activity against the contact lens paraphernalia isolate, however, it was more against the environmental strains after 12 h incubation time. The commercially available MPDS employed in this research offered minimal effectiveness against the protozoa despite the contact time. Improvement or development of new solution should consider the adjustment of the appropriate disinfectant concentration, adequate exposure time or the incorporation of novel chemical elements, which are effective against Acanthamoeba for accelerated disinfecting and more reduction of potential exposure of contact lens users to Acanthamoeba keratitis.
  20. Jeyamogan S, Khan NA, Anwar A, Shah MR, Siddiqui R
    SAGE Open Med, 2018;6:2050312118781962.
    PMID: 30034805 DOI: 10.1177/2050312118781962
    Objectives: To synthesize novel compounds belonging to Benzodioxane, Naphthalene diimide, Aminophenol derivatives and Porphyrin classes and test their potential anticancer properties.

    Methods: Several compounds were synthesized and their molecular identity was confirmed using nuclear magnetic resonance. Potential anticancer properties were determined using cytopathogenicity assays and growth inhibition assays using cervical cancer cells (HeLa). Cells were incubated with different concentrations of compounds belonging to Benzodioxane, Naphthalene diimide, Aminophenol derivatives and Porphyrins and effects were determined. HeLa cells cytopathogenicity was determined by measuring lactate dehydrogenase release using cytotoxicity detection assay. Growth inhibition assays were performed by incubating 50% semi-confluent HeLa cells with Benzodioxane, Naphthalene diimide, Aminophenol derivatives and Porphyrin compounds and HeLa cell proliferation was observed. Growth inhibition and host cell death were compared in the presence and absence of drugs.

    Results: Cytopathogenicity assays showed that the selected compounds were cytotoxic against HeLa cells, killing up to 90% of cells. Growth inhibition assays exhibited 100% growth inhibition. These effects are likely via oxidative stress, production of reactive oxygen species, changes in cytosolic and intracellular calcium/adenine nucleotide homeostasis, inhibition of ribonucleotide reductase/cyclooxygenase and/or glutathione depletion.

    Conclusions: Benzodioxane, Naphthalene diimide, Aminophenol derivatives and Porphyrins exhibited potent anticancer properties. These findings are promising and should pave the way in the rationale development of anticancer drugs. Using different cancer cell lines, future studies will determine their potential as anti-tumour agents as well as their precise molecular mode of action.

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