Displaying publications 61 - 80 of 95 in total

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  1. Walvekar S, Anwar A, Anwar A, Sridewi N, Khalid M, Yow YY, et al.
    Acta Trop, 2020 Nov;211:105618.
    PMID: 32628912 DOI: 10.1016/j.actatropica.2020.105618
    Acanthamoeba spp. are free living amoeba (FLA) which are widely distributed in nature. They are opportunistic parasites and can cause severe infections to the eye, skin and central nervous system. The advances in drug discovery and modifications in the chemotherapeutic agents have shown little improvement in morbidity and mortality rates associated with Acanthamoeba infections. The mechanism-based process of drug discovery depends on the molecular drug targets present in the signaling pathways in the genome. Synthetic libraries provide a platform for broad spectrum of activities due to their desired structural modifications. Azoles, originally a class of synthetic anti-fungal drugs, disrupt the fungal cell membrane by inhibiting the biosynthesis of ergosterol through the inhibition of cytochrome P450 dependent 14α-lanosterol, a key step of the sterol pathway. Acanthamoeba and fungi share the presence of similar sterol intermediate, as ergosterol is also the major end-product in the sterol biosynthesis in Acanthamoeba. Sterols present in the eukaryotic cell membrane are one of the most essential lipids and exhibit important structural and signaling functions. Therefore, in this review we highlight the importance of specific targeting of ergosterol present in Acanthamoebic membrane by azole compounds for amoebicidal activity. Previously, azoles have also been repurposed to report antimicrobial, antiparasitic and antibacterial properties. Moreover, by loading the azoles into nanoparticles through advanced techniques in nanotechnology, such as physical encapsulation, adsorption, or chemical conjugation, the pharmacokinetics and therapeutic index of the drugs can be significantly improved. The current review proposes an important strategy to target Acanthamoeba using synthetic libraries of azoles and their conjugated nanoparticles for the first time.
  2. Anwar A, Siddiqui R, Hameed A, Shah MR, Khan NA
    Med Chem, 2020;16(7):841-847.
    PMID: 31544702 DOI: 10.2174/1573406415666190722113412
    BACKGROUND: Acanthamoeba is an opportunistic pathogen widely spread in the environment. Acanthamoeba causes excruciating keratitis which can lead to blindness. The lack of effective drugs and its ability to form highly resistant cyst are one of the foremost limitations against successful prognosis. Current treatment involves mixture of drugs at high doses but still recurrence of infection can occur due to ineffectiveness of drugs against the cyst form. Pyridine and its natural and synthetic derivatives are potential chemotherapeutic agents due to their diverse biological activities.

    OBJECTIVE: To study the antiamoebic effects of four novel synthetic dihydropyridine (DHP) compounds against Acanthamoeba castellanii belonging to the T4 genotype. Furthermore, to evaluate their activity against amoeba-mediated host cells cytopathogenicity as well as their cytotoxicity against human cells.

    METHODS: Dihydropyridines were synthesized by cyclic dimerization of alkylidene malononitrile derivatives. Four analogues of functionally diverse DHPs were tested against Acanthamoeba castellanii by using amoebicidal, encystation and excystation assays. Moreover, Lactate dehydrogenase assays were carried out to study cytopathogenicity and cytotoxicity against human cells.

    RESULTS: These compounds showed significant amoebicidal and cysticidal effects at 50 μM concentration, whereas, two of the DHP derivatives also significantly reduced Acanthamoebamediated host cell cytotoxicity. Moreover, these DHPs were found to have low cytotoxicity against human cells suggesting a good safety profile.

    CONCLUSION: The results suggest that DHPs have potential against Acanthamoeba especially against the more resistant cyst stage and can be assessed further for drug development.

  3. Masri A, Khan NA, Zoqratt MZHM, Ayub Q, Anwar A, Rao K, et al.
    BMC Microbiol, 2021 Feb 17;21(1):51.
    PMID: 33596837 DOI: 10.1186/s12866-021-02097-2
    BACKGROUNDS: Escherichia coli K1 causes neonatal meningitis. Transcriptome studies are indispensable to comprehend the pathology and biology of these bacteria. Recently, we showed that nanoparticles loaded with Hesperidin are potential novel antibacterial agents against E. coli K1. Here, bacteria were treated with and without Hesperidin conjugated with silver nanoparticles, and silver alone, and 50% minimum inhibitory concentration was determined. Differential gene expression analysis using RNA-seq, was performed using Degust software and a set of genes involved in cell stress response and metabolism were selected for the study.

    RESULTS: 50% minimum inhibitory concentration with silver-conjugated Hesperidin was achieved with 0.5 μg/ml of Hesperidin conjugated with silver nanoparticles at 1 h. Differential genetic analysis revealed the expression of 122 genes (≥ 2-log FC, P

  4. Sam CX, Anwar AZ, Ahmad AR, Solayar GN
    Malays Orthop J, 2021 Mar;15(1):119-123.
    PMID: 33880158 DOI: 10.5704/MOJ.2103.018
    Introduction: Reverse total shoulder arthroplasty provides a surgical alternative to standard total shoulder arthroplasty for the treatment of cuff tear arthropathy, arthritis and fracture sequelae. This study aimed to assess the short-term outcomes following reverse total shoulder arthroplasty for patients in a large public hospital in Malaysia.

    Materials and Methods: We identified and performed five primary reverse total shoulder arthroplasties between 1 May 2019 and 1 June 2020. All patients were contactable and available for analysis. Assessment of functional outcomes was performed using the Constant-Murley score, the patient satisfaction score (PSS), and imaging studies. The mean follow-up from operation to the time of reporting was 9.6 months (range, 3 to 14 months).

    Results: The median age for our patients was 58 years (±11.91). The most common indication for surgery was post-traumatic arthritis, followed by rotator cuff arthropathy and osteoarthritis. The mean Constant score improved from 9.0 pre-operatively to 52.3 post-operatively at a mean of 9.6 months. The majority of the patients were satisfied with the surgery as the post-operative range of motion, especially anterior elevation and abduction, improved in four of our patients and there were no short-term complications, for example, of infection or revisions, reported at the last follow-up.

    Conclusion: This study has shown that reverse total shoulder arthroplasty can yield good short-term outcomes for the treatment of complex shoulder problems in addition to cuff tear arthropathy. It should be considered a treatment for rotator cuff tears, severe arthritis and ≥ 3 parts proximal humeral fractures.

  5. Erum H, Abid G, Anwar A, Ijaz MF, Kee DMH
    Eur J Investig Health Psychol Educ, 2021 Mar 30;11(2):321-333.
    PMID: 34708832 DOI: 10.3390/ejihpe11020024
    Family motivation as a mediating mechanism is a novel and under-researched area in the field of positive organizational scholarship. Drawing on Social Exchange Theory (SET), this study empirically validates family motivation as a mediator between family support and work engagement. The process by Hayes (2013) was used to analyze time-lagged data collected from 356 employees of the education sector. Results confirm the mediating role of family motivation in the relationship between family support and work engagement and the moderating role of calling in the relationship between family support and family motivation. This study adds to the literature of family-work enrichment accounts by validating family support as a novel antecedent for family motivation and positive attitudes. The implications of the study are discussed.
  6. Masri A, Abdelnasir S, Anwar A, Iqbal J, Numan A, Jagadish P, et al.
    Appl Microbiol Biotechnol, 2021 Apr;105(8):3315-3325.
    PMID: 33797573 DOI: 10.1007/s00253-021-11221-1
    BACKGROUND: Conducting polymer based nanocomposites are known to be effective against pathogens. Herein, we report the antimicrobial properties of multifunctional polypyrrole-cobalt oxide-silver nanocomposite (PPy-Co3O4-AgNPs) for the first time. Antibacterial activities were tested against multi-drug-resistant Gram-negative Escherichia coli (E. coli) and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) bacteria, while antiamoebic effects were assessed against opportunistic protist Acanthamoeba castellanii (A. castellanii).

    RESULTS: The ternary nanocomposite containing conducting polymer polypyrrole, cobalt oxide, and silver nanoparticles showed potent antimicrobial effects against these pathogens. The antibacterial assay showed that PPy-Co3O4-AgNPs exhibited significant bactericidal activity against neuropathogenic E. coli K1 at only 8 μg/mL as compared to individual components of the nanocomposite, whereas a 70 % inhibition of A. castellanii viability was observed at 50 μg/mL. Moreover, PPy-Co3O4-AgNPs were found to have minimal cytotoxicity against human keratinocytes HaCaT cells in vitro even at higher concentration (50 μg/mL), and also reduced the microbes-mediated cytopathogenicity against host cells.

    CONCLUSION: These results demonstrate that PPy-Co3O4-AgNPs hold promise in the development of novel antimicrobial nanomaterials for biomedical applications.

    KEY POINTS: •Synthesis of polypyrrole-cobalt oxide-silver (PPy-Co3O4-AgNPs) nanocomposite. •Antimicrobial activity of nanocomposite. •PPy-Co3O4-AgNPs hold promise for biomedical applications.

  7. 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.
  8. Rashid B, Anwar A, Shahabuddin S, Mohan G, Saidur R, Aslfattahi N, et al.
    Materials (Basel), 2021 Aug 04;14(16).
    PMID: 34442891 DOI: 10.3390/ma14164370
    The MXenes are a novel family of 2-D materials with promising biomedical activity, however, their anticancer potential is still largely unexplored. In this study, a comparative cytotoxicity investigation of Ti3C2 MXenes with polypropylene glycol (PPG), and polyethylene glycol (PEG) surface-modified 2-D Ti3C2 MXene flakes has been conducted towards normal and cancerous human cell lines. The wet chemical etching method was used to synthesize MXene followed by a simple chemical mixing method for surface modification of Ti3C2 MXene with PPG and PEG molecules. SEM and XRD analyses were performed to examine surface morphology and elemental composition, respectively. FTIR and UV-vis spectroscopy were used to confirm surface modification and light absorption, respectively. The cell lines used to study the cytotoxicity of MXene and surface-modified MXenes in this study were normal (HaCaT and MCF-10A) and cancerous (MCF-7 and A375) cells. These cell lines were also used as controls (without exposure to study material and irradiation) to measure their baseline cell viability under the same lab environment. The surface-modified MXenes exhibited a sharp reduction in cell viability towards both normal (HaCaT and MCF-10A) and cancerous (MCF-7 and A375) cells but cytotoxicity was more pronounced towards cancerous cell lines. This may be due to the difference in cell metabolism and the occurrence of high pre-existing levels of reactive oxygen species (ROS) within cancerous cells. The highest toxicity towards both normal and cancerous cell lines was observed with PEGylated MXenes followed by PPGylated and bare MXenes. The normal cell's viability was barely above 70% threshold with 250 mg/L PEGylated MXene concentration whereas PPGylated and bare MXene were less toxic towards normal cells, even at 500 mg/L concentration. Moreover, the toxicity was found to be directly related to the type of cell lines. In general, the HaCaT cell line exhibited the lowest toxicity while toxicity was highest in the case of the A375 cell line. The photothermal studies revealed high photo response for PEGylated MXene followed by PPGylated and bare MXenes. However, the PPGylated MXene's lower cytotoxicity towards normal cells while comparable toxicity towards malignant cells as compared to PEGylated MXenes makes the former a relatively safe and effective anticancer agent.
  9. Mungroo MR, Khan NA, Anwar A, Siddiqui R
    Int Microbiol, 2021 Aug 09.
    PMID: 34368912 DOI: 10.1007/s10123-021-00201-0
    Pathogenic free-living amoebae are known to cause fatal central nervous system infections with extremely high mortality rates. High selectivity of the blood-brain barrier hampers delivery of drugs and untargeted delivery of drugs can cause severe side effects. Nanovehicles can be used for targeted drug delivery across the blood-brain barrier. Inorganic nanoparticles have been explored as carriers for various biomedical applications and can be modified with various ligands for efficient targeting and cell selectivity while lipid-based nanoparticles have been extensively used in the development of both precision and colloidal nanovehicles. Nanomicelles and polymeric nanoparticles can also serve as nanocarriers and may be modified so that responsiveness of the nanoparticles and release of the loads are linked to specific stimuli. These nanoparticles are discussed here in the context of the treatment of central nervous system infections due to pathogenic amoebae. It is anticipated that these novel strategies can be utilized in tandem with novel drug leads currently in the pipeline and yield in the development of much needed treatments against these devastating parasites.
  10. Ahmed U, Anwar A, Ong SK, Anwar A, Khan NA
    Med Res Rev, 2021 Sep 02.
    PMID: 34472107 DOI: 10.1002/med.21851
    Acanthamoeba is a genus of free-living amoebae, pervasively found in the environment. Most of its pathogenic species are the causative agent of sight-threatening Acanthamoeba keratitis and fatal granulomatous amoebic encephalitis. Despite the advancements in the field of chemotherapy, treating Acanthamoeba infections is still challenging due to incomplete knowledge of the complicated pathophysiology. In case of infection, the treatment regimen for the patients is often ineffective due to delayed diagnosis, poor specificity, and side-effects. Besides the resistance of Acanthamoeba cysts to most of the drugs, the recurrence of infection further complicates the recovery. Thus, it is necessary to develop an effective treatment which can eradicate these rare, but serious infections. Based on various computational and in vitro studies, it has been established that the synthetic scaffolds such as heterocyclic compounds may act as potential drug leads for the development of antiamoebic drugs. In this review, we report different classes of synthetic compounds especially heterocyclic compounds which have shown promising results against Acanthamoeba. Moreover, the antiamoebic activities of synthetic compounds with their possible mode of actions against Acanthamoeba, have been summarized and discussed in this review.
  11. Abdelnasir S, Mungroo MR, Shahabuddin S, Siddiqui R, Khan NA, Anwar A
    ACS Chem Neurosci, 2021 Oct 06;12(19):3579-3587.
    PMID: 34545742 DOI: 10.1021/acschemneuro.1c00179
    Free-living amoebae include Acanthamoeba castellanii and Naegleria fowleri that are opportunistic protozoa responsible for life-threatening central nervous system infections with mortality rates over 90%. The rising number of cases and high mortality rates are indicative of the critical unmet need for the development of efficient drugs in order to avert future deaths. In this study, we assess the anti-amoebic capacity of a conducting polymer nanocomposite comprising polyaniline (PANI) and hexagonal boron nitride (hBN) against A. castellanii and N. fowleri. We observed significant amoebicidal and cysticidal effects using 100 μg/mL PANI/hBN (P < 0.05). Further, the nanocomposite demonstrated negligible cytotoxicity toward HaCaT and primary human corneal epithelial cells (pHCECs). In evaluating the mode of inhibition of A. castellanii due to treatment with PANI/hBN, increased intracellular reactive oxygen species (ROS) was measured and scanning microscopy visualized the formation of pores in the amoebae. Overall, this study is suggestive of the potential of the PANI/hBN nanocomposite as a promising therapy for amoeba infections.
  12. Aizuddin AN, Chan CM, Anwar AR, Ong YX, Chin KY
    Int J Gen Med, 2021;14:3251-3257.
    PMID: 34267543 DOI: 10.2147/IJGM.S316360
    Purpose: Body mass index (BMI) is used universally to define obesity. Many studies have indicated that the current BMI cutoff value for obesity may be inaccurate in identifying individuals with excess body fat (BF) and at risk for cardiovascular diseases (CVD). This study aims to assess the performance of BMI in diagnosing obesity defined by BF percentage (BF%).

    Patients and Methods: A total of 136 participants who attended an annual health screening programme were recruited. The subjects completed the health examinations, including BMI, BF% and blood pressure measurement. A receiver operating curve (ROC) analysis was conducted to determine the optimal cutoff value of BMI in classifying obesity based on BF% (>25%).

    Results: The ROC analysis revealed that the optimal BMI cutoff value in classifying subjects with obesity based on BF% was 24.8 kg/m2. The agreement between the classification scheme based on the new BMI cutoff (>24.8 kg/m2) and BF% was higher (κ=0.722) compared to the standard BMI cutoff (>27.5 kg/m2) (κ=0.532). BMI 24.8 kg/m2 also had higher sensitivity (80.0%) than 27.5 kg/m2 (56.0%) in detecting subjects with high adiposity. The new BMI cutoff also showed a sensitivity of 63.9% in identifying subjects with hypertension compared to the standard cutoff (36.1%).

    Conclusion: The current definition of obesity based on BMI value needs to be reassessed by taking BF% into account. A new BMI cutoff point, 24.8 kg/m2 for obesity, can identify a higher percentage of Malaysian at risk for CVD.

  13. Salmi MS, Ahmed U, Aslfattahi N, Rahman S, Hardy JG, Anwar A
    RSC Adv, 2022 Nov 15;12(51):33142-33155.
    PMID: 36425203 DOI: 10.1039/d2ra04944a
    Two dimensional (2D) nanomaterials display properties with significant biological utility (e.g., antimicrobial activity). In this study, MXene-functionalized graphene (FG) nanocomposites with Ti3C2T x in varying ratios (FG : Ti3C2T x , 25 : 75%, 50 : 50%, and 75 : 25%) were prepared and characterized via scanning electron microscopy, scanning electron microscopy-energy dispersive X-ray (SEM-EDX), high-resolution transmission electron microscopy (HRTEM), and zeta potential analysis. Their cytotoxicity was assessed using immortalized human keratinocytes (HaCaT) cells at three different timepoints, and antibacterial activity was assessed using Gram-positive Methicillin resistant Staphylococcus aureus, MRSA, and Gram-negative neuro-pathogenic Escherichia coli K1 (E. coli K1) in vitro. The nanomaterials and composites displayed potent antibacterial effects against both types of bacteria and low cytotoxicity against HaCaT cells at 200 μg mL-1, which is promising for their utilization for biomedical applications.
  14. Anwar A, Ma'amor A, Mahmud HNME, Basirun WJ, Abdullah I
    Turk J Chem, 2022;46(3):730-746.
    PMID: 37720623 DOI: 10.55730/1300-0527.3363
    The oxidation of ethylbenzene (EB) using tert-butyl hydroperoxide as the oxidizing agent was carried out in presence of gold nanoparticles (3 nm) supported on zinc oxide in acetonitrile solution. A higher selectivity towards acetophenone (ACP) as the major product, and a moderate selectivity towards other products such as 1-phenylethanol (PE), benzaldehyde (BZL), and benzoic acid (BzA) were observed using the prepared Au/ZnO nanocatalysts at 100 °C for 24 h. It is suggested the reaction produces an intermediate product, which is dimethylethyl-1-phenylethyl peroxide through a radical mechanism. A small amount of benzaldehyde was observed because benzaldehyde went autoxidation to form benzoic acid with the presence of oxidation agent of TBHP during reaction. The factors affecting the catalytic activity such as gold loading, calcination treatment at 300°C, type of solvent, reaction time, reaction temperature, oxidant to substrate molar ratio, catalyst weight, and solvent volume were studied. The gold nanoparticle catalyst synthesized by deposition precipitation method using urea was characterized by XRD, HRTEM, ATR-IR, XRF, and BET and offers a very selective reaction pathway for the oxidation of ethylbenzene.
  15. Mustafa S, Qiao Y, Yan X, Anwar A, Hao T, Rana S
    Front Psychol, 2022;13:956281.
    PMID: 35936293 DOI: 10.3389/fpsyg.2022.956281
    During the COVID-19 pandemic, online teaching modes were found vital to continue students' learning process, but sustainable implementation of online teaching models is an area of concern for policymakers. Psychiatrists are also eager to know students' behavior toward learning and modes of teaching during COVID-19. We have drawn a model based on the big five personality traits to study students' satisfaction with online teaching modes and their adoption intentions toward online teaching modes. We have collected data from 718 bachelor's and master's level students from four different universities. We have applied the SEM-ANN dual-stage approach to test personality traits' influence and ranked them based on their normalized importance. The results revealed that agreeableness, conscientiousness, neuroticism, and openness positively influence students' satisfaction with online teaching models, but that extraversion negatively influences their satisfaction. Agreeableness, extraversion, and neuroticism positively impact, but openness negatively influences. Conscientiousness does not affect adoption intention. Furthermore, agreeableness is the most significant, and conscientiousness is the least important factor for students to adopt online teaching modes. The findings of the study have useful perceptiveness for educational policymakers, academics, and psychiatrists.
  16. Maciver SK, Abdelnasir S, Anwar A, Siddiqui R, Khan NA
    Mol Biochem Parasitol, 2023 Feb;253:111541.
    PMID: 36603708 DOI: 10.1016/j.molbiopara.2022.111541
    Protistan parasitic infections contribute significantly to morbidity and mortality, causing more than 2 billion human infections annually. However, current treatments are often limited; due to ineffective drugs and drug resistance, thus better options are urgently required. In the present context, theranostics agents are those that offer simultaneous detection, diagnosis and even treatment of protistan parasitic diseases. "Nanotheranostics" is the term used to describe such agents, that are around 100 nm or less in size. Anti-parasitic activity of nanoparticles (NPs) has been reported, and many have useful intrinsic imaging properties, but it is perhaps their multifunctional nature that offers the greatest potential. NPs may be used as adapters onto which various subunits with different functions may be attached. These subunits may facilitate targeting parasites, coupled with toxins to eradicate parasites, and probe subunits for detection of particles and/or parasites. The modular nature of nano-platforms promises a "mix and match" approach for the construction of tailored agents by using combinations of these subunits against different protistan parasites. Even though many of the subunits have shown promise alone, these have not yet been put together convincingly enough to form working theranostics against protistan parasites. Although the clinical application of nanotheranostics to protistan parasitic infections in humans requires more research, we conclude that they offer not just a realisation of Paul Ehrlich's long imagined "magic bullet" concept, but potentially are magic bullets combined with tracer bullets.
  17. Ahmed U, Manzoor M, Qureshi S, Mazhar M, Fatima A, Aurangzeb S, et al.
    Acta Trop, 2023 Mar;239:106824.
    PMID: 36610529 DOI: 10.1016/j.actatropica.2023.106824
    Pathogenic A. castellanii and N. fowleri are opportunistic free-living amoebae. Acanthamoeba spp. are the causative agents of granulomatous amebic encephalitis (GAE) and amebic keratitis (AK), whereas Naegleria fowleri causes a very rare but severe brain infection called primary amebic meningoencephalitis (PAM). Acridinone is an important heterocyclic scaffold and both synthetic and naturally occurring derivatives have shown various valuable biological properties. In the present study, ten synthetic Acridinone derivatives (I-X) were synthesized and assessed against both amoebae for anti-amoebic and cysticidal activities in vitro. In addition, excystation, encystation, cytotoxicity, host cell pathogenicity was also performed in-vitro. Furthermore, molecular docking studies of these compounds with three cathepsin B paralogous enzymes of N. fowleri were performed in order to predict the possible docking mode with pathogen. Compound VII showed potent anti-amoebic activity against A. castellanii with IC50 53.46 µg/mL, while compound IX showed strong activity against N. fowleri in vitro with IC50 72.41 µg/mL. Compounds II and VII showed a significant inhibition of phenotypic alteration of A. castellanii, while compound VIII significantly inhibited N. fowleri cysts. Cytotoxicity assessment showed that these compounds caused minimum damage to human keratinocyte cells (HaCaT cells) at 100 µg/mL, while also effectively reduced the cytopathogenicity of Acanthamoeba to HaCaT cells. Moreover, Cathepsin B protease was investigated in-silico as a new molecular therapeutic target for these compounds. All compounds showed potential interactions with the catalytic residues. These results showed that acridine-9(10H)-one derivatives, in particular compounds II, VII, VIII and IX hold promise in the development of therapeutic agents against these free-living amoebae.
  18. Abdelnasir S, Mungroo MR, Chew J, Siddiqui R, Khan NA, Ahmad I, et al.
    ACS Omega, 2023 Mar 07;8(9):8237-8247.
    PMID: 36910978 DOI: 10.1021/acsomega.2c06050
    Primary amoebic meningoencephalitis and granulomatous amoebic encephalitis are distressing infections of the central nervous system caused by brain-eating amoebae, namely, Naegleria fowleri and Acanthamoeba spp., respectively, and present mortality rates of over 90%. No single drug has been approved for use against these infections, and current therapy is met with an array of obstacles including high toxicity and limited specificity. Thus, the development of alternative effective chemotherapeutic agents for the management of infections due to brain-eating amoebae is a crucial requirement to avert future mortalities. In this paper, we synthesized a conducting polymer-based nanocomposite entailing polyaniline (PANI) and molybdenum disulfide (MoS2) and explored its anti-trophozoite and anti-cyst potentials against Acanthamoeba castellanii and Naegleria fowleri. The intracellular generation of reactive oxygen species (ROS) and ultrastructural appearances of amoeba were also evaluated with treatment. Throughout, treatment with the 1:2 and 1:5 ratios of PANI/MoS2 at 100 μg/mL demonstrated significant anti-amoebic effects toward A. castellanii as well as N. fowleri, appraised to be ROS mediated and effectuate physical alterations to amoeba morphology. Further, cytocompatibility toward human keratinocyte skin cells (HaCaT) and primary human corneal epithelial cells (pHCEC) was noted. For the first time, polymer-based nanocomposites such as PANI/MoS2 are reported in this study as appealing options in the drug discovery for brain-eating amoebae infections.
  19. Serour G, Ghaly M, Saifuddeen SM, Anwar A, Isa NM, Chin AHB
    New Bioeth, 2023 Jun;29(2):108-120.
    PMID: 36427532 DOI: 10.1080/20502877.2022.2142094
    An exciting development in the field of assisted reproductive technologies is In Vitro Gametogenesis (IVG) that enables production of functional gametes from stem cells in the laboratory. Currently, development of this technology is still at an early stage and has demonstrated to work only in rodents. Upon critically examining the ethical dimensions of various possible IVG applications in human fertility treatment from a Sunni Islamic perspective, together with benefit-harm (maslahah-mafsadah) assessment; it is concluded that utilization of IVG, once its efficacy and safety are guaranteed, could be permissible by strictly adhering to Islamic ethical principles related to marriage, biological/genetic relatedness, sexual intercourse, and moral status of the embryo/fetus versus that of the gamete. As a result, IVG will be acceptable for treating primary infertility, age-related infertility, and preventing genetic diseases. However, it will be unacceptable for application in posthumous reproduction, donor gametes, genetic enhancement, and procreation in same-sex couples.
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