Displaying publications 21 - 40 of 161 in total

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  1. Siddiqui R, Ali IK, Cope JR, Khan NA
    Acta Trop, 2016 Dec;164:375-394.
    PMID: 27616699 DOI: 10.1016/j.actatropica.2016.09.009
    Naegleria fowleri is a protist pathogen that can cause lethal brain infection. Despite decades of research, the mortality rate related with primary amoebic meningoencephalitis owing to N. fowleri remains more than 90%. The amoebae pass through the nose to enter the central nervous system killing the host within days, making it one of the deadliest opportunistic parasites. Accordingly, we present an up to date review of the biology and pathogenesis of N. fowleri and discuss needs for future research against this fatal infection.
  2. Siddiqui R, Abjani F, Yeo CI, Tiekink ER, Khan NA
    J Negat Results Biomed, 2017 Apr 03;16(1):6.
    PMID: 28366172 DOI: 10.1186/s12952-017-0070-7
    BACKGROUND: Gold compounds have shown promise in the treatment of non-communicable diseases such as rheumatoid arthritis and cancer, and are considered of value as anti-microbial agents against Gram-negative and Gram-positive bacteria, and have anti-parasitic properties against Schistosoma mansoni, Trypanosoma brucei, Plasmodium falciparum, Leishmania infantinum, Giardia lamblia, and Entamoeba histolytica. They are known to affect enzymatic activities that are required for the cellular respiration processes.

    METHODS: Anti-amoebic effects of phosphanegold(I) thiolates were tested against clinical isolate of A. castellanii belonging to the T4 genotype by employing viability assays, growth inhibition assays, encystation assays, excystation assays, and zymographic assays.

    RESULTS: The treatment of A. castellanii with the phosphanegold(I) thiolates tested (i) had no effect on the viability of A. castellanii as determined by Trypan blue exclusion test, (ii) did not affect amoebae growth using PYG growth medium, (iii) did not inhibit cellular differentiation, and (iv) had no effect on the extracellular proteolytic activities of A. castellanii.

    CONCLUSION: Being free-living amoeba, A. castellanii is a versatile respirator and possesses respiratory mechanisms that adapt to various aerobic and anaerobic environments to avoid toxic threats and adverse conditions. For the first time, our findings showed that A. castellanii exhibits resistance to the toxic effects of gold compounds and could prove to be an attractive model to study mechanisms of metal resistance in eukaryotic cells.

  3. Siddiqui R, Rajendran K, Abdella B, Ayub Q, Lim SY, Khan NA
    Parasitol Res, 2020 Jul;119(7):2351-2358.
    PMID: 32451717 DOI: 10.1007/s00436-020-06711-6
    Naegleria fowleri causes a deadly infection known as primary amoebic meningoencephalitis (PAM). To our knowledge, there are very few transcriptome studies conducted on these brain-eating amoebae, despite rise in the number of cases. Although the Naegleria genome has been sequenced, currently, it is not well annotated. Transcriptome level studies are needed to help understand the pathology and biology of this fatal parasitic infection. Recently, we showed that nanoparticles loaded with the flavonoid Hesperidin (HDN) are potential novel antimicrobial agents. N. fowleri trophozoites were treated with and without HDN-conjugated with silver nanoparticles (AgNPs) and silver only, and then, 50% minimum inhibitory concentration (MIC) was determined. The results revealed that the MIC of HDN-conjugated AgNPs was 12.5 microg/mL when treated for 3 h. As no reference genome exists for N. fowleri, de novo RNA transcriptome analysis using RNA-Seq and differential gene expression analysis was performed using the Trinity software. Analysis revealed that more than 2000 genes were differentially expressed in response to N. fowleri treatment with HDN-conjugated AgNPs. Some of the genes were linked to oxidative stress response, DNA repair, cell division, cell signalling and protein synthesis. The downregulated genes were linked with processes such as protein modification, synthesis of aromatic amino acids, when compared with untreated N. fowleri. Further transcriptome studies will lead to understanding of genetic mechanisms of the biology and pathogenesis and/or the identification of much needed drug candidates.
  4. Siddiqui R, Khan NA
    Exp Parasitol, 2017 Dec;183:133-136.
    PMID: 28807757 DOI: 10.1016/j.exppara.2017.08.006
    Bacterial infections have remained significant despite our advances in the development of a plethora of disinfectants as well as antimicrobial chemotherapy. This is in part due to our incomplete understanding of the prevalence of bacterial pathogens in the environmental and clinical settings. Several lines of evidence suggest that Acanthamoeba is one of the most ubiquitous/resilient protists that also acts as a host/reservoir for pathogenic microbes. Thus targeting the hardy host, which harbour microbial pathogens, offer a potential avenue to counter infection transmission, particularly hospital/community-acquired infections. This will complement existing approach of applying disinfectants that are targeted against bacterial pathogens directly.
  5. Siddiqui R, Jeyamogan S, Ali SM, Abbas F, Sagathevan KA, Khan NA
    Exp Parasitol, 2017 Dec;183:194-200.
    PMID: 28917711 DOI: 10.1016/j.exppara.2017.09.008
    Crocodiles exist in unsanitary environments, feed on rotten meat, are often exposed to heavy metals such as arsenic, cadmium, cobalt, chromium, mercury, nickel, lead, selenium, tolerate high levels of radiation, and are amid the very few species to survive the catastrophic Cretaceous-Tertiary extinction event, nonetheless they can live for up to a 100 years. Moreover, as they live in unhygienic conditions, they regularly come across pathogens. Logically, we postulate that crocodiles possess mechanisms to defend themselves from noxious agents as well as protecting themselves from pathogens. To test this hypothesis, various organ lysates and serum of Crocodylus palustris were prepared. Amoebicidal assays were performed using Acanthamoeba castellanii belonging to the T4 genotype. Cytotoxicity assays were performed using Prostate cancer cells culture by measuring lactate dehydrogenase release as a marker for cell death. Growth inhibition assays were performed to determine the growth inhibitory effects of various organ lysates. Serum and heart lysates of Crocodylus palustris exhibited powerful anti-tumor activity exhibiting more than 70% Prostate cancer cell death (P 
  6. Siddiqui R, Yee Ong TY, Jung SY, Khan NA
    Exp Parasitol, 2017 Dec;183:128-132.
    PMID: 28823705 DOI: 10.1016/j.exppara.2017.08.005
    Among the genus Streptococcus, S. pyogenes and S. pneumoniae are the major causes of pharyngitis, impetigo, pneumonia and meningitis in humans. Streptococcus spp. are facultative anaerobes that are nutritionally fastidious, yet survive in the environment and target the predisposed population. Antibacterial disinfectants have been partially effective only, indicating the need for novel preventative measures and to understand mechanisms of bacterial resistance. Acanthamoeba is a free-living protist that is known to harbour microbial pathogens, provide shelter, and assist in their transmission to susceptible population. The overall aim of this study was to determine whether S. pyogenes and S. pneumoniae can interact with A. castellanii by associating, invading, and surviving inside trophozoites and cysts. It was observed that both S. pyogenes and S. pneumoniae were able to associate as well as invade and/or taken up by the phagocytic A. castellanii trophozoite. Notably, S. pyogenes and S. pneumoniae survived the encystation process, avoided phagocytosis, multiplied, and exhibited higher recovery from the mature cysts, compared with the trophozoite stage (approximately 2 bacteria per amoebae ratio for cyst stage versus 0.02 bacteria per amoeba ration for trophozoite stage). As Acanthamoeba cysts are resilient and can disperse through the air, A. castellanii can act as a vector in providing shelter, facilitating growth and possibly genetic exchanges. In addition, these interactions may contribute to S. pyogenes and S. pneumoniae survival in harsh environments, and transmission to susceptible population and possibly affecting their virulence. Future studies will determine the molecular mechanisms associated with Acanthamoeba interactions with Streptococcus and the evolution of pathogenic bacteria and in turn expedite the discovery of novel therapeutic and/or preventative measures.
  7. 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.
  8. Siddiqui R, Maciver SK, Anuar TS, Khan NA
    Am J Vet Res, 2023 Aug 01;84(8).
    PMID: 37353216 DOI: 10.2460/ajvr.23.03.0061
    OBJECTIVE: The objective of this study was to determine bacterial flora throughout the gastrointestinal tract of a saltwater crocodile (Crocodylus porosus) using 16S rRNA gene analysis.

    ANIMALS: A convention on international trade in endangered species (CITES) of wild fauna and flora registered crocodile farm, provided a healthy male saltwater crocodile, Crocodylus porosus for this study.

    PROCEDURES: Three samples were taken from the oral cavity, 3 samples from the proximal region of the small intestine (jejunum), and 3 samples from the distal part of the large intestine of the gastrointestinal tract of C. porosus were obtained using sterile cotton swabs. Next, swabs were placed in 15 mL sterile centrifuge tubes, individually, and kept on ice for immediate transportation to the laboratory. This was followed by 16S rRNA gene analysis using specific primers (341F-CCTAYGGGRBGCASCAG, and 806R-GGACTACNNGGGTATCTAAT). Amplicons were sequenced on Illumina paired-end platform, and bacterial gastrointestinal communities, the relative abundance of taxa, and principal component and coordinate analysis were performed.

    RESULTS: The findings revealed that bacterial community structures from differing regions exhibited several differences. The number of observed bacterial operational taxonomic units (OTUs) was 153 in the oral cavity, 239 in the small intestine, and 119 in the large intestine of C. porosus. The small intestine reflects the highest richness. In contrast, the large intestine exhibited the least richness of microbial communities. Relative abundance of taxa showed that Proteobacteria, Bacteroidetes, and Firmicutes were dominant in all 3 sample sites. Pseudomonas differed in the oral cavity and the large intestine, with the latter exhibiting less distribution of Pseudomonas. Stenotrophomonas and Castellaniella were higher in the oral cavity, while the relative abundance of Comamonas and Salmonella was higher in the small intestine. Conversely, the relative abundance of Salmonella and Pannonibacter was augmented in the large intestine.

    CLINICAL RELEVANCE: For the first time, this study demonstrates the bacterial diversity along the segments of the gastrointestinal tract of C. porosus. Bacterial flora varies throughout the gastrointestinal tract. Although further studies using large cohorts are warranted; however, our findings suggest that microbiome composition may have the potential as a biomarker in determining the overall health and well-being of C. porosus.

  9. 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.
  10. Shahbaz MS, Anwar A, Saad SM, Kanwal, Anwar A, Khan KM, et al.
    Parasitol Res, 2020 Jul;119(7):2327-2335.
    PMID: 32476058 DOI: 10.1007/s00436-020-06710-7
    Acanthamoeba castellanii is a free-living amoeba which can cause a blinding keratitis and fatal granulomatous amoebic encephalitis. The treatment of Acanthamoeba infections is challenging due to formation of cyst. Quinazolinones are medicinally important scaffold against parasitic diseases. A library of nineteen new 3-aryl-6,7-dimethoxyquinazolin-4(3H)-one derivatives was synthesized to evaluate their antiamoebic activity against Acanthamoeba castellanii. One-pot synthesis of 3-aryl-6,7-dimethoxyquinazolin-4(3H)-ones (1-19) was achieved by reaction of 2-amino-4,5-dimethoxybenzoic acid, trimethoxymethane, and different substituted anilines. These compounds were purified and characterized by standard chromatographic and spectroscopic techniques. Antiacanthamoebic activity of these compounds was determined by amoebicidal, encystation, excystation and host cell cytopathogenicity in vitro assays at concentrations of 50 and 100 μg/mL. The IC50 was found to be between 100 and 50 μg/mL for all the compounds except compound 5 which did not exhibit amoebicidal effects at these concentrations. Furthermore, lactate dehydrogenase assay was also performed to evaluate the in vitro cytotoxicity of these compounds against human keratinocyte (HaCaT) cells. The results revealed that eighteen out of nineteen derivatives of quinazolinones significantly decreased the viability of A. castellanii. Furthermore, eighteen out of nineteen tested compounds inhibited the encystation and excystation, as well as significantly reduced the A. castellanii-mediated cytopathogenicity against human cells. Interestingly, while tested against human normal cell line HaCaT keratinocytes, all compounds did not exhibit any overt cytotoxicity. Furthermore, a detailed structure-activity relationship is also studied to optimize the most potent hit from these synthetic compounds. This report presents several potential lead compounds belonging to 3-aryl-6,7-dimethoxyquinazolin-4(3H)-one derivatives for drug discovery against infections caused by Acanthamoeba castellanii.
  11. Schutte AE, Jafar TH, Poulter NR, Damasceno A, Khan NA, Nilsson PM, et al.
    Cardiovasc Res, 2023 Mar 31;119(2):381-409.
    PMID: 36219457 DOI: 10.1093/cvr/cvac130
    Raised blood pressure (BP) is the leading cause of preventable death in the world. Yet, its global prevalence is increasing, and it remains poorly detected, treated, and controlled in both high- and low-resource settings. From the perspective of members of the International Society of Hypertension based in all regions, we reflect on the past, present, and future of hypertension care, highlighting key challenges and opportunities, which are often region-specific. We report that most countries failed to show sufficient improvements in BP control rates over the past three decades, with greater improvements mainly seen in some high-income countries, also reflected in substantial reductions in the burden of cardiovascular disease and deaths. Globally, there are significant inequities and disparities based on resources, sociodemographic environment, and race with subsequent disproportionate hypertension-related outcomes. Additional unique challenges in specific regions include conflict, wars, migration, unemployment, rapid urbanization, extremely limited funding, pollution, COVID-19-related restrictions and inequalities, obesity, and excessive salt and alcohol intake. Immediate action is needed to address suboptimal hypertension care and related disparities on a global scale. We propose a Global Hypertension Care Taskforce including multiple stakeholders and societies to identify and implement actions in reducing inequities, addressing social, commercial, and environmental determinants, and strengthening health systems implement a well-designed customized quality-of-care improvement framework.
  12. Rehman IU, Wu DB, Ahmed R, Khan NA, Rahman AU, Munib S, et al.
    Medicine (Baltimore), 2018 08;97(31):e10764.
    PMID: 30075491 DOI: 10.1097/MD.0000000000010764
    BACKGROUND: Pruritus adds to the complications of chronic kidney disease (CKD) patient and a well-recognized complication among the CKD patients. Majority of the patients on hemodialysis experience a generalized pruritus and patients reported being moderately to extremely disturbed by at least one of the sleep-related condition. This study aim to investigate the effectiveness of zolpidem 10 mg and acupressure therapy on foot acupoints to improve the sleep quality and overall quality of life among hemodialysis patients suffering from CKD-associated pruritus.

    METHODS: A multicentered, open-label, parallel group, prospective randomized controlled trial among patients suffering from CKD-associated pruritus with sleep disturbance, after randomization into control, and intervention group to be held at North West General Hospital and Research Center Peshawar, Pakistan and Institute of Kidney Diseases Peshawar, Pakistan.

    RESULTS: The primary outcome is to investigate the effectiveness of zolpidem 10 mg and acupressure therapy on foot acupoints to improve the sleep quality and overall quality of life among hemodialysis patients suffering from CKD-associated pruritus. After baseline assessment by Urdu version of 5D itch scale and Urdu version of Pittsburgh Sleep Quality Index (PSQI) and Urdu EQ-5D 3L, the intervention group will be given zolpidem 10 mg oral tablets and control group with acupressure on both foots on KI-1 acupoints for total of 6 minutes. Assessment will be done at weeks 4 and 8 from baseline by using Urdu version of 5D itch scale and Urdu version of PSQI and Urdu EQ-5D 3L, whereas safety profiling of zolpidem 10 mg tablet at week 6 from baseline and acupressure acceptability at week 6 from baseline. Analysis of covariance will be used to examine the differences in treatment effects between the intervention and control groups.

    CONCLUSION: Improvement of sleep quality and quality of life among patients with CKD-associated pruritus requires great importance. This study aims to improve the quality of sleep and quality of life among patients with hemodialysis suffering from CKD-associated pruritus.

  13. Rehman IU, Ahmed R, Rahman AU, Wu DBC, Munib S, Shah Y, et al.
    Medicine (Baltimore), 2021 May 28;100(21):e25995.
    PMID: 34032717 DOI: 10.1097/MD.0000000000025995
    BACKGROUND: Chronic kidney disease (CKD)-associated pruritus (CKD-aP) contributes to poor quality of life, including reduced sleep quality and poor sleep quality is a source of patient stress and is linked to lower health-related quality of life. This study aimed to investigate the effectiveness of zolpidem 10 mg and acupressure therapy on foot acupoints to improve the sleep quality and overall quality of life among hemodialysis patients suffering from CKD-aP.

    METHOD: A multicenter, prospective, randomized, parallel-design, open label interventional study to estimate the effectiveness of zolpidem (10 mg) oral tablets versus acupressure on sleep quality and quality of life in patients with CKD-aP on hemodialysis. A total of 58 hemodialysis patients having sleep disturbance due to CKD-aP completed the entire 8-week follow-up. The patients were divided into a control (acupressure) group of 28 patients and an intervention (zolpidem) group of 30 patients.

    RESULTS: A total of 58 patients having CKD-aP and sleep disturbance were recruited. In the control group there was a reduction in the PSQI score with a mean ± SD from 12.28 ± 3.59 to 9.25 ± 3.99, while in the intervention group the reduction in PSQI score with a mean ± SD was from 14.73 ± 4.14 to 10.03 ± 4.04 from baseline to endpoint. However, the EQ5D index score and EQ-visual analogue scale (VAS) at baseline for the control group with a mean ± SD was 0.49 ± 0.30 and 50.17 ± 8.65, respectively, while for the intervention group the values were 0.62 ± 0.26 and 47.17 ± 5.82, respectively. The mean EQ5D index score in the control group improved from 0.49 ± 0.30 to 0.53 ± 0.30, but in the intervention group there was no statistical improvement in mean EQ5D index score from 0.62 ± 0.26 to 0.62 ± 0.27 from baseline to week 8. The EQ 5D improved in both groups and the EQ-VAS score was 2.67 points higher at week 8 as compared to baseline in the control group, while in the intervention group the score was 3.33 points higher at week 8 as compared to baseline. Comparing with baseline, the PSQI scores were significantly reduced after week 4 and week 8 (P =  

  14. Reginald K, Wong YR, Shah SMR, Teh KF, Freddy Jalin EJ, Khan NA
    Microbes Infect, 2021 07 28;23(9-10):104876.
    PMID: 34332091 DOI: 10.1016/j.micinf.2021.104876
    BACKGROUND: Insects models are excellent models of the innate immune system, as they are free from the influences of vertebrate adaptive immunity. Crickets are hemimetabolous insects belonging to the order Orthopteran order that have not been as extensively characterized as other holometabolous insects, and may provide new insights into the insect immune responses. In this study, we aim to characterize the innate immune responses of the common house cricket, Acheta domesticus in response to a human pathogenic bacterium E. coli K1.

    METHODS: Crickets were injected with sterile buffer, live E. coli K1 or heat-killed E. coli K1. Physiological effects such as mortality and weight change of the crickets were determined 24-, 48- and 72-h post injection while immunological effects such as hemocyte counts, bacteremia, phenoloxidase and lysozyme activity of the crickets were measured at 2- and 24-h post-injection.

    RESULTS: The injection of E. coli K1 in crickets resulted in >85% mortality 3-days post injection, accompanied by significant weight loss. E. coli K1 injection caused a significant increase in both phenoloxidase and lysozyme activities in cricket hemolymphs 24-h post injection. Live E. coli K1 injected crickets resulted in a significant reduction in circulating hemocytes 24-h post injection which was not observed in other treatment groups. This was consistent with the resolution of bacteremia observed 24-h post infection in live E. coli K1 injected crickets.

    CONCLUSION: Our study provides new insights on the innate immune response to pathogenic E. coli K1 in a cricket model.

  15. Razzaq OA, Rehman DU, Khan NA, Ahmadian A, Ferrara M
    Results Phys, 2021 Jan;20:103715.
    PMID: 33398241 DOI: 10.1016/j.rinp.2020.103715
    In present time, the whole world is in the phase of war against the deadly pandemic COVID'19 and working on different interventions in this regard. Variety of strategies are taken into account from ground level to the state to reduce the transmission rate. For this purpose, the epidemiologists are also augmenting their contribution in structuring such models that could depict a scheme to diminish the basic reproduction number. These tactics also include the awareness campaigns initiated by the stakeholders through digital, print media and etc. Analyzing the cost and profit effectiveness of these tactics, we design an optimal control dynamical model to study the proficiency of each strategy in reducing the virulence of COVID'19. The aim is to illustrate the memory effect on the dynamics of COVID'19 with and without prevention measures through fractional calculus. Therefore, the structure of the model is in line with generalized proportional fractional derivative to assess the effects at each chronological change. Awareness about using medical mask, social distancing, frequent use of sanitizer or cleaning hand and supportive care during treatment are the strategies followed worldwide in this fight. Taking these into consideration, the optimal objective function proposed for the surveillance mitigation of COVID'19, is contemplated as the cost function. The effect analysis is supported through graphs and tabulated values. In addition, sensitivity inspection of basic reproduction number is also carried out with respect to different values of fractional index and cost function. Ultimately, social distancing and supportive care of infected are found to be significant in decreasing the basic reproduction number more rapidly.
  16. Rao K, Abdullah M, Ahmed U, Wehelie HI, Shah MR, Siddiqui R, et al.
    Arch Microbiol, 2024 Mar 04;206(4):134.
    PMID: 38433145 DOI: 10.1007/s00203-024-03854-3
    Acanthamoeba castellanii are opportunistic pathogens known to cause infection of the central nervous system termed: granulomatous amoebic encephalitis, that mostly effects immunocompromised individuals, and a sight threatening keratitis, known as Acanthamoeba keratitis, which mostly affects contact lens wearers. The current treatment available is problematic, and is toxic. Herein, an amphiphilic star polymer with AB2 miktoarms [A = hydrophobic poly(ℇ-Caprolacton) and B = hydrophilic poly (ethylene glycol)] was synthesized by ring opening polymerization and CuI catalyzed azide-alkyne cycloaddition. Characterization by 1H and 13C NMR spectroscopy, size-exclusion chromatography and fluorescence spectroscopy was accomplished. The hydrophobic drug itraconazole (ITZ) was incorporated in self-assembled micellar structure of AB2 miktoarms through co-solvent evaporation. The properties of ITZ loaded (ITZ-PCL-PEG2) and blank micelles (PCL-PEG2) were investigated through zeta sizer, scanning electron microscopy and Fourier-transform infrared spectroscopy. Itraconazole alone (ITZ), polymer (DPB-PCL), empty polymeric micelles (PCL-PEG2) alone, and itraconazole loaded in polymeric micelles (ITZ-PCL-PEG2) were tested for anti-amoebic potential against Acanthamoeba, and the cytotoxicity on human cells were determined. The polymer was able to self-assemble in aqueous conditions and exhibited low value for critical micelle concentration (CMC) 0.05-0.06 µg/mL. The maximum entrapment efficiency of ITZ was 68%. Of note, ITZ, DPB, PCL-PEG2 and ITZ-PCL-PEG2 inhibited amoebae trophozoites by 37.34%, 36.30%, 35.77%, and 68.24%, respectively, as compared to controls. Moreover, ITZ-PCL-PEG2 revealed limited cytotoxicity against human keratinocyte cells. These results are indicative that ITZ-PCL-PEG2 micelle show significantly better anti-amoebic effects as compared to ITZ alone and thus should be investigated further in vivo to determine its clinical potential.
  17. Ramachandran S, Verma AK, Dev K, Goyal Y, Bhatt D, Alsahli MA, et al.
    Oxid Med Cell Longev, 2021;2021:5563746.
    PMID: 34336101 DOI: 10.1155/2021/5563746
    With over a million deaths every year around the world, lung cancer is found to be the most recurrent cancer among all types. Nonsmall cell lung carcinoma (NSCLC) amounts to about 85% of the entire cases. The other 15% owes it to small cell lung carcinoma (SCLC). Despite decades of research, the prognosis for NSCLC patients is poorly understood with treatment options limited. First, this article emphasises on the part that tumour microenvironment (TME) and its constituents play in lung cancer progression. This review also highlights the inflammatory (pro- or anti-) roles of different cytokines (ILs, TGF-β, and TNF-α) and chemokine (CC, CXC, C, and CX3C) families in the lung TME, provoking tumour growth and subsequent metastasis. The write-up also pinpoints recent developments in the field of chemokine biology. Additionally, it covers the role of extracellular vesicles (EVs), as alternate carriers of cytokines and chemokines. This allows the cytokines/chemokines to modulate the EVs for their secretion, trafficking, and aid in cancer proliferation. In the end, this review also stresses on the role of these factors as prognostic biomarkers for lung immunotherapy, apart from focusing on inflammatory actions of these chemoattractants.
  18. Rajendran K, Anwar A, Khan NA, Aslam Z, Raza Shah M, Siddiqui R
    ACS Chem Neurosci, 2020 08 19;11(16):2431-2437.
    PMID: 31347828 DOI: 10.1021/acschemneuro.9b00289
    Naegleria fowleri (N. fowleri) causes primary amoebic meningoencephalitis (PAM) which almost always results in death. N. fowleri is also known as "brain-eating amoeba" due to its literal infestation of the brain leading to an inflammatory response in the brain tissues. Currently, there is no single drug that is available to treat PAM, and most treatments are combinations of antifungal, anticancer, and anti-inflammatory drugs. Recently nanotechnology has gained attention in chemotherapeutic research converging on drug delivery, while oleic acid (OA) has shown positive effects on the human immune system and inflammatory processes. In continuation of our recent research in which we reported the effects of oleic acid conjugated with silver nanoparticles (OA-AgNPs) against free-living amoeba Acanthamoeba castellanii, in this report, we show their antiamoebic effects against N. fowleri. OA alone and its nanoconjugates were tested against the amoeba by using amoebicidal and host cell cytopathogenicity assays. Trypan blue exclusion assay was used to determine cell viability. The results revealed that OA-AgNPs exhibited significantly enhanced antiamoebic effects (P < 0.05) against N. fowleri as compared to OA alone. Evidently, lactate dehydrogenase release shows reduced N. fowleri-mediated host cell cytotoxicity. Based on our study, we anticipate that further studies on OA-AgNPs could potentially provide an alternative treatment of PAM.
  19. Rajendran K, Anwar A, Khan NA, Shah MR, Siddiqui R
    ACS Chem Neurosci, 2019 06 19;10(6):2692-2696.
    PMID: 30970208 DOI: 10.1021/acschemneuro.9b00111
    Primary amoebic meningoencephalitis (PAM), a deadly brain infection, is caused by brain-eating amoeba Naegleria fowleri. The current first line of treatment against PAM is a mixture of amphotericin B, rifampin, and miltefosine. Since, no single effective drug has been developed so far, the mortality rate is above 95%. Moreover, severe adverse side effects are associated with these drugs. Nanotechnology has provided several advances in biomedical applications especially in drug delivery and diagnosis. Herein, for the first time we report antiamoebic properties of cinnamic acid (CA) and gold nanoparticles conjugated with CA (CA-AuNPs) against N. fowleri. CA-AuNPs were successfully synthesized by sodium borohydride reduction of tetrachloroauric acid. Size and morphology were determined by atomic force microscopy (AFM) while the surface plasmon resonance band was analyzed by ultraviolet-visible (UV-vis) spectrophotometry for the characterization of the nanoparticles. Amoebicidal and cytopathogenicity (host cell cytotoxicity) assays revealed that both CA and CA-AuNPs displayed significant anti- N. fowleri properties ( P < 0.05), whereas nanoparticles conjugation further enhanced the anti- N. fowleri effects of CA. This study established a potential drug lead, while CA-AuNPs appear to be promising candidate for drug discovery against PAM.
  20. Rajendran K, Anwar A, Khan NA, Siddiqui R
    ACS Chem Neurosci, 2017 12 20;8(12):2626-2630.
    PMID: 29206032 DOI: 10.1021/acschemneuro.7b00430
    The overall aim of this study was to determine whether conjugation with silver nanoparticles enhances effects of available drugs against primary amoebic meningoencephalitis due to Naegleria fowleri. Amphotericin B, Nystatin, and Fluconazole were conjugated with silver nanoparticles, and synthesis was confirmed using UV-visible spectrophotometry. Atomic force microscopy determined their size in range of 20-100 nm. To determine amoebicidal effects, N. fowleri were incubated with drugs-conjugated silver nanoparticles, silver nanoparticles alone, and drugs alone. The findings revealed that silver nanoparticles conjugation significantly enhanced antiamoebic effects of Nystatin and Amphotericin B but not Fluconazole at micromolar concentrations, compared with the drugs alone. For the first time, our findings showed that silver nanoparticle conjugation enhances efficacy of antiamoebic drugs against N. fowleri. Given the rarity of the disease and challenges in developing new drugs, it is hoped that modifying existing drugs to enhance their antiamoebic effects is a useful avenue that holds promise in improving the treatment of brain-eating amoebae infection due to N. fowleri.
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