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Fulltext Gold Nanoparticles Conjugation Enhances Antiacanthamoebic Properties of Nystatin, Fluconazole and Amphotericin B

Anwar A, Siddiqui R, Raza Shah M, Ahmed Khan N

J Microbiol Biotechnol, 2019 Jan 28;29(1):171-177.
PMID: 30415525 DOI: 10.4014/jmb.1805.05028

Parasitic infections have remained a significant burden on human and animal health. In part, this is due to lack of clinically-approved, novel antimicrobials and a lack of interest by the pharmaceutical industry. An alternative approach is to modify existing clinically-approved drugs for efficient delivery formulations to ensure minimum inhibitory concentration is achieved at the target site. Nanotechnology offers the potential to enhance the therapeutic efficacy of drugs through modification of nanoparticles with ligands. Amphotericin B, nystatin, and fluconazole are clinically available drugs in the treatment of amoebal and fungal infections. These drugs were conjugated with gold nanoparticles. To characterize these gold-conjugated drug, atomic force microscopy, ultraviolet-visible spectrophotometry and Fourier transform infrared spectroscopy were performed. These drugs and their gold nanoconjugates were examined for antimicrobial activity against the protist pathogen, Acanthamoeba castellanii of the T4 genotype. Moreover, host cell cytotoxicity assays were accomplished. Cytotoxicity of these drugs and drug-conjugated gold nanoparticles was also determined by lactate dehydrogenase assay. Gold nanoparticles conjugation resulted in enhanced bioactivity of all three drugs with amphotericin B producing the most significant effects against Acanthamoeba castellanii (p ＜ 0.05). In contrast, bare gold nanoparticles did not exhibit antimicrobial potency. Furthermore, amoebae treated with drugs-conjugated gold nanoparticles showed reduced cytotoxicity against HeLa cells. In this report, we demonstrated the use of nanotechnology to modify existing clinically-approved drugs and enhance their efficacy against pathogenic amoebae. Given the lack of development of novel drugs, this is a viable approach in the treatment of neglected diseases.
Shaping a greener future: The role of geopolitical risk, renewable energy and financial development on environmental sustainability using the LCC hypothesis

Wang W, Balsalobre-Lorente D, Anwar A, Adebayo TS, Cong PT, Quynh NN, et al.

J Environ Manage, 2024 Apr;357:120708.
PMID: 38552512 DOI: 10.1016/j.jenvman.2024.120708

The recent progress report of Sustainable Development Goals (SDG) 2023 highlighted the extreme reactions of environmental degradation. This report also shows that the current efforts for achieving environmental sustainability (SDG 13) are inadequate and a comprehensive policy agenda is needed. However, the present literature has highlighted several determinants of environmental degradation but the influence of geopolitical risk on environmental quality (EQ) is relatively ignored. To fill this research gap and propose a inclusive policy structure for achieving the sustainable development goals. This study is the earliest attempt that delve into the effects o of geopolitical risk (GPR), financial development (FD), and renewable energy consumption (REC) on load capacity factor (LCF) under the framework of load capacity curve (LCC) hypothesis for selected Asian countries during 1990-2020. In this regard, we use several preliminary sensitivity tests to check the features and reliability of the dataset. Similarly, we use panel quantile regression for investigating long-run relationships. The factual results affirm the existence of the LCC hypothesis in selected Asian countries. Our findings also show that geopolitical risk reduces environmental quality whereas financial development and REC increase environmental quality. Drawing from the empirical findings, this study suggests a holistic policy approach for achieving the targets of SDG 13 (climate change).
Applications of photodynamic therapy in keratitis

Anwar A, Khan NA, Alharbi AM, Alhazmi A, Siddiqui R

Int Ophthalmol, 2024 Mar 15;44(1):140.
PMID: 38491335 DOI: 10.1007/s10792-024-03062-4

Keratitis is corneal inflammatory disease which may be caused by several reason such as an injury, allergy, as well as a microbial infection. Besides these, overexposure to ultraviolet light and unhygienic practice of contact lenses are also associated with keratitis. Based on the cause of keratitis, different lines of treatments are recommended. Photodynamic therapy is a promising approach that utilizes light activated compounds to instigate either killing or healing mechanism to treat various diseases including both communicable and non-communicable diseases. This review focuses on clinically-important patent applications and the recent literature for the use of photodynamic therapy against keratitis.
Nanovehicles in the improved treatment of infections due to brain-eating amoebae

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.
Combination Therapy of Clinically Approved Antifungal Drugs Is Enhanced by Conjugation with Silver Nanoparticles

Hussain MA, Ahmed D, Anwar A, Perveen S, Ahmed S, Anis I, et al.

Int Microbiol, 2019 Jun;22(2):239-246.
PMID: 30810990 DOI: 10.1007/s10123-018-00043-3

Silver nanoparticles (SN) have been recently developed as a new class of antimicrobial agents against numerous pathogenic microorganisms. SN have also been used as efficient drug delivery systems and have been linked with increasing drug potency. Here, we demonstrated the enhanced antifungal efficacy of nystatin (NYT) and fluconazole (FLU) after conjugation with SN. The antifungal bioactivity of NYT- and FLU-coated SN was evaluated against Candida albicans ATCC 10231 and Aspergillus brasiliensis ATCC 16404 by the agar tube dilution method. The aim of this study was to determine and compare the antifungal efficacy of NYT and FLU with their SN and, finally, the combination of both nanoparticles as NYT-SN + FLU-SN against pathogenic fungi. The results indicated that all test samples showed a dose-dependent response against tested fungi. SN significantly enhanced the antifungal effects of NYT and FLU as compared to drugs alone. We observed a remarkable increase in the percent inhibition of both fungi (90-100%) when treated with a combination of both nanoparticles NYT-SN + FLU-SN at 200 μg/mL only. Furthermore, the morphological modifications occurred at the surface of fungal species were also analyzed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). While tested against primary human cell line, all SN showed negligible cytotoxicity. Hence, these results suggest that the combination of SN with NYT and FLU may have clinical implications in the treatment of fungal infections. However, in vivo studies are needed before recommending the use of these nanoparticles safely in clinical situations.
Alpha-Mangostin and its nano-conjugates induced programmed cell death in Acanthamoeba castellanii belonging to the T4 genotype

Ahmed U, Ong SK, Tan KO, Khan KM, Khan NA, Siddiqui R, et al.

Int Microbiol, 2023 Nov 28.
PMID: 38015290 DOI: 10.1007/s10123-023-00450-1

Acanthamoeba are free living amoebae that are the causative agent of keratitis and granulomatous amoebic encephalitis. Alpha-Mangostin (AMS) is a significant xanthone; that demonstrates a wide range of biological activities. Here, the anti-amoebic activity of α-Mangostin and its silver nano conjugates (AMS-AgNPs) were evaluated against pathogenic A. castellanii trophozoites and cysts in vitro. Amoebicidal assays showed that both AMS and AMS-AgNPs inhibited the viability of A. castellanii dose-dependently, with an IC50 of 88.5 ± 2.04 and 20.2 ± 2.17 μM, respectively. Both formulations inhibited A. castellanii-mediated human keratinocyte cell cytopathogenicity. Functional assays showed that both samples caused apoptosis through the mitochondrial pathway and reduced mitochondrial membrane potential and ATP production, while increasing reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH) cytochrome-c reductase in the cytosol. Whole transcriptome sequencing of A. castellanii showed the expression of 826 genes, with 447 genes being up-regulated and 379 genes being down-regulated post treatment. The Kyoto Encyclopedia of Genes and Genomes analysis showed that the majority of genes were linked to apoptosis, autophagy, RAP1, AGE-RAGE and oxytocin signalling pathways. Seven genes (PTEN, H3, ARIH1, SDR16C5, PFN, glnA GLUL, and SRX1) were identified as the most significant (Log2 (FC) value 4) for molecular mode of action in vitro. Future in vivo studies with AMS and nanoconjugates are needed to realize the clinical potential of this work.
Performance of Body Mass Index in Identifying Obesity Defined by Body Fat Percentage and Hypertension Among Malaysian Population: A Retrospective Study

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.
Fulltext Incidence of Helicobacter pylori Infection using (13) C- Urea BreathTest and Gastric Biopsy Culture

Khairul, A.J., Anwar, A., Ramelah, M.

International Medical Journal Malaysia, 2007;6(2):1-8.
MyJurnal

Background: (13) C – urea breath test (UBT) is sensitive and specific for detection of Helicobacter pylori (H. pylori) infection. Gastric biopsy culture for H. pylori confirms the diagnosis. Here, we analyzed data of all patients who were investigated for H. pylori infection using both tests throughout the year 2005. Materials and Methods : Retrospective data of 377 patients between the ages of 17 – 88 were identified through endoscopy records from January to December 2005. Upper endoscopy, UBT and gastric biopsy culture were performed on all patients simultaneously during each endoscopy session. Patients who had positive UBT and biopsy culture for H. pylori were treated with triple therapy of PPI, amoxicillin and clarithromycin for one week. A repeat of UBT was done at one-month post therapy. Results and Analysis: Twenty-eight patients on the list had no available data on UBT and were omitted from the analysis. Ethnic group Chinese comprised of 45.4% (n=163), followed by Malay, 37.3% (n=134), Indian, 10.6% (n=38) and others, 3.9% (n=14). UBT was positive in 23.7% (n=85)(figure1). H. pylori culture was positive in 19.2% (n=69)(figure1). Sixteen patients with UBT positive had H. pylori culture negative, 18.8% (n=16/85)(figure2). Five patients with H. pylori culture positive had UBT negative, 7.2% (n=5/69)(figure3). Ethnic group Indian had the highest incidence of UBT positive, 47.4% (n=18/38), followed by Others (Sikhs and foreigners) 42.8% (n=6/14), the Chinese 27.6% (n=45/163) and the Malays 11.6% (n= 16/138). UBT positive was the highest in the age group of 50 and above, 64.7% (n=55/85), followed by the age group between 30 to 49, 21.2% (n=18/85) and the age group of 29 and below, 14.5% (n=12/85). Out of the 85 UBT positive patients 91.8% (n=78/85)(figure4) of them responded to the conventional one week of triple therapy (PPI, amoxicillin, clarithromycin) with negative UBT at one-month post therapy compared to only 8.2% (n=7/85)(figure4) who failed with positive UBT at one-month post therapy.
Fulltext Mechanisms of Colorectal Cancer Cell Growth and Metastasis Inhibition By Carp-1 Functional Mimetic-4

Abdelkader E. Ashour, Anwar A. Almuslim, Sheikh F. Ahmad, Sabry M. Attia, Rehan Ahmed, Ashok Kumar, et al.

IIUM Medical Journal Malaysia, 2019;18(102):44-0.
MyJurnal

Colorectal cancer (CRC) constitutes one of the most aggressive malignancies worldwide and in Malaysia. Due to high recurrence rate and toxic side effects associated with radiation and chemotherapies, new agents are urgently needed. CARP-1 is a peri-nuclear phospho-protein which plays a dynamic role in regulating cell growth and apoptosis. CARP-1 functional mimetics (CFMs) are a class of compounds that stimulate CARP-1. CFM-4, a lead compound, was shown to suppress growth and metastasis of various cancers, other than CRC. We hypothesized that CFM-4 inhibits proliferation and metastasis in CRC. Materials and method: CFM-4 anti-cancer effects of on CRC cells were investigated using MTT assay, Annexin V/Propidium iodide (PI) apoptosis assay, cell cycle analysis, quantitative real-time PCR (qRT-PCR) and Western blotting. Antimetastatic activities were assessed by migration, colony formation and invasion assays. Results: CFM-4 inhibited CRC cell proliferation and was much more potent than the classical anti-CRC 5-fluorouracil. These effects were shown to be mediated at least in part by stimulating apoptosis, as indicated in our Annexin V/PI assay results. Cell cycle analysis showed that CFM-4 induced G2/M phase arrest. Molecularly, qRT-PCR results revealed that CFM-4 promoted intrinsic apoptosis by upregulating expression of caspase-8 and -9 , p53, PUMA and Noxa, and stimulated extrinsic apoptosis by enhancing expression of death receptors (DR4 and DR5). CFM-4 upregulated NF- k B signaling inhibitor A20-binding inhibitor protein and the PI3K negative regulator PTEN. Western blot analysis results revealed that CFM-4 enhanced expression of CARP1, caspase-8 and executioner caspase-3. Metastatic properties of the CRC cells were reduced by CFM-4 through blocking their capabilities to form colonies, migrate and invade through the matrix-coated membranes. Conclusion: The potent antitumor and anti-metastatic properties of CFM-4 against CRC are due to collective pro-apoptotic, anti-proliferative and anti-metastatic activities. Together our data warrants further investigations of CFM-4 as potential anti-tumor agent for CRC malignancy and metastasis.
Fulltext An international multidisciplinary consensus statement on MAFLD and the risk of CVD

Zhou XD, Targher G, Byrne CD, Somers V, Kim SU, Chahal CAA, et al.

Hepatol Int, 2023 Aug;17(4):773-791.
PMID: 37204656 DOI: 10.1007/s12072-023-10543-8

BACKGROUND: Fatty liver disease in the absence of excessive alcohol consumption is an increasingly common condition with a global prevalence of ~ 25-30% and is also associated with cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies its pathogenesis, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been proposed for this condition. MAFLD is closely intertwined with obesity, type 2 diabetes mellitus and atherogenic dyslipidemia, which are established cardiovascular risk factors. Unlike CVD, which has received attention in the literature on fatty liver disease, the CVD risk associated with MAFLD is often underestimated, especially among Cardiologists.
METHODS AND RESULTS: A multidisciplinary panel of fifty-two international experts comprising Hepatologists, Endocrinologists, Diabetologists, Cardiologists and Family Physicians from six continents (Asia, Europe, North America, South America, Africa and Oceania) participated in a formal Delphi survey and developed consensus statements on the association between MAFLD and the risk of CVD. Statements were developed on different aspects of CVD risk, ranging from epidemiology to mechanisms, screening, and management.
CONCULSIONS: The expert panel identified important clinical associations between MAFLD and the risk of CVD that could serve to increase awareness of the adverse metabolic and cardiovascular outcomes of MAFLD. Finally, the expert panel also suggests potential areas for future research.
Fulltext Potential anti-amoebic effects of synthetic 1,4-benzothiazine derivatives against Acanthamoeba castellanii

Alishba, Ahmed U, Taha M, Khan NA, Salar U, Khan KM, et al.

Heliyon, 2024 Jan 15;10(1):e23258.
PMID: 38205285 DOI: 10.1016/j.heliyon.2023.e23258

A rare but lethal central nervous system disease known as granulomatous amoebic encephalitis (GAE) and potentially blinding Acanthamoeba keratitis are diseases caused by free-living Acanthamoeba. Currently, no therapeutic agent can completely eradicate or prevent GAE. Synthetic compounds are a likely source of bioactive compounds for developing new drugs. This study synthesized seventeen 1,4-benzothiazine derivatives (I -XVII) by a base-catalyzed one-pot reaction of 2-amino thiophenol with substituted bromo acetophenones. Different spectroscopic techniques, such as EI-MS, 1H-, and 13C NMR (only for the new compounds), were used for the structural characterization and conformation of compounds. These compounds were assessed for the first time against Acanthamoeba castellanii. All compounds showed anti-amoebic potential in vitro against A. castellanii, reducing its ability to encyst and excyst at 100 μM. Compounds IX, X, and XVI showed the most potent activities among all derivatives and significantly reduced the viability to 5.3 × 104 (p
Immortalization of epithelial cells in oral carcinogenesis as revealed by genome-wide array comparative genomic hybridization: A meta-analysis

Vincent-Chong VK, Salahshourifar I, Razali R, Anwar A, Zain RB

Head Neck, 2016 04;38 Suppl 1:E783-97.
PMID: 25914319 DOI: 10.1002/hed.24102

BACKGROUND: This purpose of this meta-analysis study was to identify the most frequent and potentially significant copy number alteration (CNA) in oral carcinogenesis.
METHODS: Seven oral squamous cell carcinoma (OSCC)-related publications, corresponding to 312 samples, were identified for this meta-analysis. The data were analyzed in a 4-step process that included the genome assembly coordination of multiple platforms, assignment of chromosomal position anchors, calling gains and losses, and functional annotation analysis.
RESULTS: Gains were more frequent than losses in the entire dataset. High-frequency gains were identified in chromosomes 5p, 14q, 11q, 7p, 17q, 20q, 8q, and 3q, whereas high-frequency losses were identified in chromosomes 3p, 8p, 6p, 18q, and 4q. Ingenuity pathway analysis showed that the top biological function was associated with immortalization of the epithelial cells (p = 1.93E-04).
CONCLUSION: This study has identified multiple recurrent CNAs that are involved in various biological annotations associated with oral carcinogenesis. © 2015 Wiley Periodicals, Inc. Head Neck 38: E783-E797, 2016.
Distinct pattern of chromosomal alterations and pathways in tongue and cheek squamous cell carcinoma

Vincent-Chong VK, Karen-Ng LP, Abdul Rahman ZA, Yang YH, Anwar A, Zakaria Z, et al.

Head Neck, 2014 Sep;36(9):1268-1278.
PMID: 31615169 DOI: 10.1002/hed.23448

BACKGROUND: The purpose of this study was to investigate the cause of behavioral difference between tongue and cheek squamous cell carcinomas (SCCs) by verifying the copy number alterations (CNAs).
METHODS: Array comparative genomic hybridization (aCGH) was used to profile unique deletions and amplifications that are involved with tongue and cheek SCC, respectively. This was followed by pathway analysis relating to CNA genes from both sites.
RESULTS: The most frequently amplified regions in tongue SCC were 4p16.3, 11q13.4, and 13q34; whereas the most frequently deleted region was 19p12. For cheek SCC, the most frequently amplified region was identified on chromosome 9p24.1-9p23; whereas the most common deleted region was located on chromosome 8p23.1. Further analysis revealed that the most significant unique pathway related to tongue and cheek SCCs was the cytoskeleton remodeling and immune response effect on the macrophage differentiation pathway.
CONCLUSION: This study has showed the different genetic profiles and biological pathways between tongue and cheek SCCs. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1268-1278, 2014.
Fulltext Digital Students' Satisfaction With and Intention to Use Online Teaching Modes, Role of Big Five Personality Traits

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.
Synthetic nanoparticle-conjugated bisindoles and hydrazinyl arylthiazole as novel antiamoebic agents against brain-eating amoebae

Kanwal, Mungroo MR, Anwar A, Ali F, Khan S, Abdullah MA, et al.

Exp Parasitol, 2020 Nov;218:107979.
PMID: 32866583 DOI: 10.1016/j.exppara.2020.107979

Balamuthia mandrillaris and Naegleria fowleri are free-living amoebae that can cause life-threatening infections involving the central nervous system. The high mortality rates of these infections demonstrate an urgent need for novel treatment options against the amoebae. Considering that indole and thiazole compounds possess wide range of antiparasitic properties, novel bisindole and thiazole derivatives were synthesized and evaluated against the amoebae. The antiamoebic properties of four synthetic compounds i.e., two new bisindoles (2-Bromo-4-(di (1H-indol-3-yl)methyl)phenol (denoted as A1) and 2-Bromo-4-(di (1H-indol-3-yl)methyl)-6-methoxyphenol (A2)) and two known thiazole (4-(3-Nitrophenyl)-2-(2-(pyridin-3-ylmethylene)hydrazinyl)thiazole (A3) and 4-(Biphenyl-4-yl)-2-(2-(1-(pyridin-4-yl)ethylidene)hydrazinyl)thiazole (A4)) were evaluated against B. mandrillaris and N. fowleri. The ability of silver nanoparticle (AgNPs) conjugation to enrich antiamoebic activities of the compounds was also investigated. The synthetic heterocyclic compounds demonstrated up to 53% and 69% antiamoebic activities against B. mandrillaris and N. fowleri respectively, while resulting in up to 57% and 68% amoebistatic activities, respectively. Antiamoebic activities of the compounds were enhanced by up to 71% and 51% against B. mandrillaris and N. fowleri respectively, after conjugation with AgNPs. These compounds exhibited potential antiamoebic effects against B. mandrillaris and N. fowleri and conjugation of synthetic heterocyclic compounds with AgNPs enhanced their activity against the amoebae.
Metformin-coated silver nanoparticles exhibit anti-acanthamoebic activities against both trophozoite and cyst stages

Anwar A, Soomaroo A, Anwar A, Siddiqui R, Khan NA

Exp Parasitol, 2020 Aug;215:107915.
PMID: 32461112 DOI: 10.1016/j.exppara.2020.107915

Acanthamoeba castellanii is an opportunistic protozoan responsible for serious human infections including Acanthamoeba keratitis and granulomatous amoebic encephalitis. Despite advances in antimicrobial therapy and supportive care, infections due to Acanthamoeba are a major public concern. Current methods of treatment are not fully effective against both the trophozoite and cyst forms of A. castellanii and are often associated with severe adverse effects, host cell cytotoxicity and recurrence of infection. Therefore, there is an urgent need to develop new therapeutic approaches for the treatment and management of Acanthamoebic infections. Repurposing of clinically approved drugs is a viable avenue for exploration and is particularly useful for neglected and rare diseases where there is limited interest by pharmaceutical companies. Nanotechnology-based drug delivery systems offer promising approaches in the biomedical field, particularly in diagnosis and drug delivery. Herein, we conjugated an antihyperglycemic drug, metformin with silver nanoparticles and assessed its anti-acanthamoebic properties. Characterization by ultraviolet-visible spectrophotometry and atomic force microscopy showed successful formation of metformin-coated silver nanoparticles. Amoebicidal and amoebistatic assays revealed that metformin-coated silver nanoparticles reduced the viability and inhibited the growth of A. castellanii significantly more than metformin and silver nanoparticles alone at both 5 and 10 μM after 24 h incubation. Metformin-coated silver nanoparticles also blocked encystation and inhibited the excystation in Acanthamoeba after 72 h incubation. Overall, the conjugation of metformin with silver nanoparticles was found to enhance its antiamoebic effects against A. castellanii. Furthermore, the pretreatment of A. castellanii with metformin and metformin-coated silver nanoparticles for 2 h also reduced the amoebae-mediated host cell cytotoxicity after 24 h incubation from 73% to 10% at 10 μM, indicating that the drug-conjugated silver nanoparticles confer protection to human cells. These findings suggest that metformin-coated silver nanoparticles hold promise in the improved treatment and management of Acanthamoeba infections.
Novel antiacanthamoebic compounds belonging to quinazolinones

Anwar A, Shahbaz MS, Saad SM, Kanwal, Khan KM, Siddiqui R, et al.

Eur J Med Chem, 2019 Nov 15;182:111575.
PMID: 31415900 DOI: 10.1016/j.ejmech.2019.111575

We report one-pot synthesis of a series of new 3-aryl-8-methylquinazolin-4(3H)-ones (QNZ) and their antimicrobial activity against Acanthamoeba castellanii belonging to T4 genotype. A library of fifteen synthetic derivatives of QNZs was synthesized, and their structural elucidation was performed by using nuclear magnetic resonance (NMR) spectroscopy and electron impact mass spectrometry (EI-MS). Elemental analyses and high-resolution mass spectrometry data of all derivatives were found to be in agreeable range. Amoebicidal assays performed at concentrations ranging from 50 to 100 μg/mL revealed that all derivatives of QNZ significantly decreased the viability of A. castellanii and QNZ 2, 5, 8, and 13 were found to have efficient antiamoebic effects. Field emission scanning electron microscopy (FESEM) imaging of amoeba treated with compounds 5 and 15 showed that these compounds cause structural alterations on the walls of A. castellanii. Furthermore, several QNZs inhibited the encystation and excystationas as well as abolished A. castellanii-mediated host cells cytopathogenicity in human cells. Whereas, these QNZs showed negligible cytotoxicity when tested against human cells in vitro. Hence, this study identified potential lead molecules having promising properties for drug development against A. castellanii. A brief structure-activity relationship is also developed to optimize the hit of most potent compounds from the library. To the best of our knowledge, it is first of its kind medicinal chemistry approach on a single class of compounds i.e., quinazolinone against keratitis and brain infection causing free-living amoeba, A. castellanii.
Fulltext My Family Stands Behind Me: Moderated Mediation Model of Family Support and Work Engagement

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.
Impact of transportation infrastructure and urbanization on environmental pollution: evidence from novel wavelet quantile correlation approach

Malik MU, Rehman ZU, Sharif A, Anwar A

Environ Sci Pollut Res Int, 2024 Jan;31(2):3014-3030.
PMID: 38079035 DOI: 10.1007/s11356-023-31197-x

In terms of achieving sustainable development goals (SDGs), the developing economies are facing many issues, and one of the key issues is environmental degradation. Being a developing economy, Pakistan is also experiencing thought-provoking impacts of global warming and still far away from the ideal track of sustainable development. For addressing environment-related issue and achieving the targets of SDGs, a policy-level reorientation might be necessary. In this view, this study investigates the impact of economic growth, transport infrastructure, urbanization, financial development, and renewable energy consumption on CO2 emissions by using the data of Pakistan during 1990-2020. For this purpose, we use novel wavelet quantile correlation approach. The empirical results of wavelet quantile correlation approach demonstrate that economic growth, transport infrastructure, urbanization, and financial development are responsible for environmental pollution. Whereas, result also claims that renewable energy consumption is a useful tool for reducing environmental pollution in Pakistan. Moreover, the results of FMOLS approach show that 1% increase in economic growth, transportation infrastructure, urbanization, and financial development increases CO2 emissions by 0.240, 0.010, 0.478, and 0.102%, respectively. However, 1% increase in renewable energy usage reduces CO2 emission by 1.083%. Based on the empirical outcomes, this study proposes comprehensive policy framework for achieving the targets of SDG 7 (clean energy), SDG 8 (economic growth), SDG 11 (sustainable cities and communities), and SDG 13 (climate action).
From brown to green: are Asian economies on the right path? Assessing the role of green innovations and geopolitical risk on environmental quality

Khan KA, Cong PT, Thang PD, Uyen PTM, Anwar A, Abbas A

Environ Sci Pollut Res Int, 2024 Jan 17.
PMID: 38231329 DOI: 10.1007/s11356-023-31613-2

Preserving the sustainability of the natural environment has emerged as a critical focus on policy agendas worldwide. Therefore, this study examines the relationship between environmental quality and key determinants, focusing on geopolitical risk (GPR), green innovations (GI), economic growth, FDI, renewable energy consumption, and urbanization. Dataset is used for the time period of 1990-2020 across selected Asian economies including China, India, Japan, Malaysia, and South Korea. Using load capacity factor (LCF) as a comprehensive proxy for environmental quality, the research utilizes panel quantile regression (QR) to provide empirical outcomes. Results of panel QR method reveal a negative impact of economic growth and GPR on LCF. On the other hand, green innovation, FDI, and renewable energy are found as supportive factors to boost environmental quality. In addition, urbanization also shows positive linkage with LCF. The application of Fully Modified Ordinary Least Squares (FMOLS) and Dynamic Ordinary Least Squares (DOLS) further validates the robustness of the findings. Adoption of green innovations, practicing sustainable growth patterns, transition toward cleaner energy practices, and integrated urban planning are advocated to enhance environmental quality among Asian nations. Based on empirical findings study suggests comprehensive policy measures that can help in achieving sustainable development goals (SDGs) including SDG-7 (energy efficiency), SDG-8 (sustainable economic growth), SDG-11 (sustainable cities), and SDG-13 (climate action) among Asian countries.

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