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Öğe Acute stress and gut microbiome: a potential in vivo rodent model to study molecular and pathological mechanisms(Future Sci Ltd, 2023) Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed[Abstract Not Available]Öğe Alpha-Mangostin and its nano-conjugates induced programmed cell death in Acanthamoeba castellanii belonging to the T4 genotype(Springer, 2023) Ahmed, Usman; Ong, Seng-Kai; Tan, Kuan Onn; Khan, Khalid Mohammed; Khan, Naveed Ahmed; Siddiqui, Ruqaiyyah; Alawfi, Bader SaleemAcanthamoeba 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 alpha-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 mu M, 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.Öğe Anti-amoebic activity of a series of benzofuran/benzothiophene derivatives against acanthamoeba castellanii belonging to the T4 genotype(2022) Akbar, Noor; El-Gamal, Mohammed, I; Zaraei, Seyed-Omar; Saeed, Balsam Qubais; Khan, Naveed Ahmed; Siddiqui, RuqaiyyahAims: To determine the anti-amoebic activity of benzofuran/benzothiophene-possessing compounds against Acanthamoeba castellanii of the T4 genotype. Method and results: A series of benzofuran/benzothiophene-possessing compounds were tested for their anti-amoebic activities, in particular, to block encystation and excystation processes in amoebae. Cytotoxicity of the compounds were evaluated using lactate dehydrogenase (LDH) assays. The amoebicidal assay results revealed significant anti-amoebic effects against A. castellanii. Compounds 1p and 1e showed the highest amoebicidal activity, eliminating 68% and 64% of the amoebae, respectively. These compounds remarkably repressed both the encystation and excystation processes in A. castellanii. Furthermore, the selected compounds presented minimal cytotoxic properties against human cells, as well as considerably abridged amoeba-mediated cytopathogenicity when compared to the amoebae alone. Conclusions: Our findings show that benzofuran/benzothiophene derivatives depict potent anti-amoebic activities; thus these compounds should be used as promising and novel agents in the rationale development of therapeutic strategies against Acanthamoeba infections.Öğe The anti-amoebic potential of carboxamide derivatives containing sulfonyl or sulfamoyl moieties against brain-eating Naegleria fowleri(Springer, 2023) Akbar, Noor; Siddiqui, Ruqaiyyah; El-Gamal, Mohammed I.; Zaraei, Seyed-Omar; Alawfi, Bader S.; Khan, Naveed AhmedNaegleria fowleri is a free-living thermophilic flagellate amoeba that causes a rare but life-threatening infection called primary amoebic meningoencephalitis (PAM), with a very high fatality rate. Herein, the anti-amoebic potential of carboxamide derivatives possessing sulfonyl or sulfamoyl moiety was assessed against pathogenic N. fowleri using amoebicidal, cytotoxicity and cytopathogenicity assays. The results from amoebicidal experiments showed that derivatives dramatically reduced N. fowleri viability. Selected derivatives demonstrated IC50 values at lower concentrations; 1j showed IC50 at 24.65 mu M, while 1k inhibited 50% amoebae growth at 23.31 mu M. Compounds with significant amoebicidal effects demonstrated limited cytotoxicity against human cerebral microvascular endothelial cells. Finally, some derivatives mitigated N. fowleri-instigated host cell death. Ultimately, this study demonstrated that 1j and 1k exhibited potent anti-amoebic activity and ought to be looked at in future studies for the development of therapeutic anti-amoebic pharmaceuticals. Further investigation is required to determine the clinical relevance of our findings.Öğe Antiamoebic properties of ceftriaxone and zinc-oxide-cyclodextrin-conjugated ceftriaxone(MDPI, 2022) Makhlouf, Zinb; Akbar, Noor; Khan, Naveed Ahmed; Shah, Muhammad Raza; Alharbi, Ahmad M.; Alfahemi, Hasan; Siddiqui, RuqaiyyahAcanthamoeba castellanii is a ubiquitous free-living amoeba capable of instigating keratitis and granulomatous amoebic encephalitis in humans. Treatment remains limited and inconsistent. Accordingly, there is a pressing need for novel compounds. Nanotechnology has been gaining attention for enhancing drug delivery and reducing toxicity. Previous work has shown that various antibiotic classes displayed antiamoebic activity. Herein, we employed two antibiotics: ampicillin and ceftriaxone, conjugated with the nanocarrier zinc oxide and beta-cyclodextrin, and tested them against A. castellanii via amoebicidal, amoebistatic, encystment, excystment, cytopathogenicity, and cytotoxicity assays at a concentration of 100 mu g/mL. Notably, zinc oxide beta-cyclodextrin ceftriaxone significantly inhibited A. castellanii growth and cytopathogenicity. Additionally, both zinc oxide beta-cyclodextrin ceftriaxone and ceftriaxone markedly inhibited A. castellanii encystment. Furthermore, all the tested compounds displayed negligible cytotoxicity. However, minimal anti-excystment or amoebicidal effects were observed for the compounds. Accordingly, this novel nanoconjugation should be employed in further studies in hope of discovering novel anti-Acanthamoeba compounds.Öğe Antiamoebic properties of Methyltrioctylammonium chloride based deep eutectic solvents(Elsevier Ltd., 2022) Siddiqui, Ruqaiyyah; Makhlouf,Zinb; Akbar, Noor; Khamis, Mustafa; Ibrahim, Taleb; Khan, Amir Sada; Khan, Naveed AhmedAntiamoebic properties of Methyltrioctylammonium chloride based deep eutectic solventsÖğe Antibacterial effects of quercetagetin are significantly enhanced upon conjugation with chitosan engineered copper oxide nanoparticles(Springer, 2024) Alvi, Adeelah; Alqassim, Saif; Khan, Naveed Ahmed; Khatoon, Bushra; Akbar, Noor; Kawish, Muhammad; Faizi, ShaheenThe development of antibiotic alternatives that entail distinctive chemistry and modes of action is necessary due to the threat posed by drug resistance. Nanotechnology has gained increasing attention in recent years, as a vehicle to enhance the efficacy of existing antimicrobials. In this study, Chitosan copper oxide nanoparticles (CHI-CuO) were synthesized and were further loaded with Quercetagetin (QTG) to achieve the desired (CHI-CuO-QTG). Size distribution, zeta potential and morphological analysis were accomplished. Next, the developed CHI-CuO-QTG was assessed for synergistic antibacterial properties, as well as cytotoxic attributes. Bactericidal assays revealed that CHI-CuO conjugation showed remarkable effects and enhanced QTG effects against a range of Gram + ve and Gram - ve bacteria. The MIC50 of QTG against S. pyogenes was 107 mu g/mL while CHI-CuO-QTG reduced it to 9 mu g/mL. Similar results were observed when tested against S. pneumoniae. Likewise, the MIC50 of QTG against S. enterica was 38 mu g/mL while CHI-CuO-QTG reduced it to 7 mu g/mL. For E. coli K1, the MIC50 of QTG was 42 mu g/mL while with CHI-CuO-QTG it was 23 mu g/mL. Finally, the MIC50 of QTG against S. marcescens was 98 mu g/mL while CHI-CuO-QTG reduced it to 10 mu g/mL. Notably, the CHI-CuO-QTG nano-formulation showed limited damage when tested against human cells using lactate dehydrogenase release assays. Importantly, bacterial-mediated human cell damage was reduced by prior treatment of bacteria using drug nano-formulations. These findings are remarkable and clearly demonstrate that drug-nanoparticle formulations using nanotechnology is an important avenue in developing potential therapeutic interventions against microbial infections.Öğe Antibacterial Properties of Ethacridine Lactate and Sulfmethoxazole Loaded Functionalized Graphene Oxide Nanocomposites(Mdpi, 2023) Jabri, Tooba; Khan, Naveed Ahmed; Makhlouf, Zinb; Akbar, Noor; Gul, Jasra; Shah, Muhammad Raza; Siddiqui, RuqaiyyahThe emergence of drug-resistant bacterial strains that reduce the effectiveness of antimicrobial agents has become a major ongoing health concern in recent years. It is therefore necessary to find new antibacterials with broad-spectrum activity against both Gram-positive and Gram-negative bacteria, and/or to use nanotechnology to boost the potency of already available medications. In this research, we examined the antibacterial efficacy of sulfamethoxazole and ethacridine lactate loaded two-dimensional glucosamine functionalized graphene-based nanocarriers against a range of bacterial isolates. Graphene oxide was first functionalized with glucosamine, which as a carbohydrate moiety can render hydrophilic and biocompatible characters to the GO surface, and subsequently loaded with ethacridine lactate and sulfamethoxazole. The resulting nanoformulations had distinct, controllable physiochemical properties. By analyzing the formulation using Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (PXRD), a thermogravimetric analysis (TGA), zetasizer, and a morphological analysis using Scanning Electron Microscopy and Atomic Force Microscopy, researchers were able to confirm the synthesis of nanocarriers. Both nanoformulations were tested against Gram-negative bacteria, including Escherichia coli K1, Serratia marcescens, Pseudomonas aeruginosa, Salmonella enterica, as well as Gram-positive bacteria, including Bacillus cereus, Streptococcus pyogenes, and Streptococcus pneumoniae. Importantly, ethacridine lactate and its nanoformulations exhibited significant antibacterial properties against all bacteria tested in this study. When tested for minimum inhibitory concentration (MIC), the results were remarkable and revealed that ethacridine lactate presented MIC90 at 9.7 mu g/mL against S. enteric, and MIC90 at 6.2 mu g/mL against B. cereus. Notably, ethacridine lactate and its nanoformulations showed limited toxicity effects against human cells using lactate dehydrogenase assays. Overall, the results revealed that ethacridine lactate and its nanoformulations possess antibacterial activities against various Gram-negative and Gram-positive bacteria and that nanotechnology can be employed for the targeted delivery of effective drugs without harming the host tissue.Öğe Antimicrobial Activity of Novel Deep Eutectic Solvents(Mdpi, 2023) Akbar, Noor; Khan, Naveed Ahmed; Ibrahim, Taleb; Khamis, Mustafa; Khan, Amir Sada; Alharbi, Ahmad M.; Alfahemi, HasanHerein, we utilized several deep eutectic solvents (DES) that were based on hydrogen donors and hydrogen acceptors for their antibacterial application. These DES were tested for their bactericidal activities against Gram-positive (Streptococcus pyogenes, Bacillus cereus, Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus) and Gram-negative (Escherichia coli K1, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Serratia marcescens) bacteria. Using lactate dehydrogenase assays, DES were evaluated for their cytopathic effects towards human cells. Results from antibacterial tests revealed that DES prepared from the combination of methyl-trioctylammonium chloride and glycerol (DES-4) and DES prepared form methyl-trioctylammonium chloride and fructose (DES-11) at a 2 mu L dose showed broad-spectrum antibacterial behavior and had the highest bactericidal activity. Moreover, DES-4 showed 40% and 68% antibacterial activity against P. aeruginosa and E. coli K1, respectively. Similarly, DES-11 eliminated 65% and 61% E. coli K1 and P. aeruginosa, respectively. Among Gram-positive bacteria, DES-4 showed important antibacterial activity, inhibiting 75% of B. cereus and 51% of S. pneumoniae. Likewise, DES-11 depicted 70% B. cereus and 50% S. pneumoniae bactericidal effects. Finally, the DES showed limited cytotoxic properties against human cell lines with the exception of the DES prepared from Methyltrioctylammonium chloride and Citric acid (DES-10), which had 88% cytotoxic effects. These findings suggest that DES depict potent antibacterial efficacies and cause minimal damage to human cells. It can be concluded that the selected DES in this study could be utilized as valuable and novel antibacterial drugs against bacterial infections. In future work, the mechanisms for bactericides and the cytotoxicity effects of these DES will be investigated.Öğe Applications of photodynamic therapy in keratitis(Springer, 2024) Anwar, Ayaz; Khan, Naveed Ahmed; Alharbi, Ahmad M.; Alhazmi, Ayman; Siddiqui, RuqaiyyahKeratitis 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.Öğe Applications of Polyaniline-Based Molybdenum Disulfide Nanoparticles against Brain-Eating Amoebae(Amer Chemical Soc, 2023) Abdelnasir, Sumayah; Mungroo, Mohammad Ridwane; Chew, Jactty; Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed; Ahmad, Irfan; Shahabuddin, SyedPrimary 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 mu g/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.Öğe Azole and 5-nitroimidazole based nanoformulations are potential antiamoebic drug candidates against brain-eating amoebae(Oxford Univ Press, 2023) Akbar, Noor; Hussain, Kashif; Khalid, Maria; Siddiqui, Ruqaiyyah; Shah, Muhammad Raza; Khan, Naveed AhmedAim Herein, the anti-parasitic activity of azoles (fluconazole and itraconazole) and 5-nitroimdazole (metronidazole) against the brain-eating amoebae: Naegleria fowleri and Balamuthia mandrillaris was elucidated. Methods and results Azoles and 5-nitroimidazole based nanoformulations were synthesized and characterized using a UV-visible spectrophotometer, atomic force microscopy, and fourier transform infrared spectroscopy. H-1-NMR, EI-MS, and ESI-MS were performed to determine their molecular mass and elucidate their structures. Their size, zeta potential, size distribution, and polydispersity index (PDI) were assessed. Amoebicidal assays revealed that all the drugs and their nanoformulations, (except itraconazole) presented significant anti-amoebic effects against B. mandrillaris, while all the treatments indicated notable amoebicidal properties against N. fowleri. Amoebicidal effects were radically enhanced upon conjugating the drugs with nanoparticles. The IC50 values for KM-38-AgNPs-F, KM-20-AgNPs-M, and KM-IF were 65.09, 91.27, and 72.19 mu g.mL-1, respectively, against B. mandrillaris. Whereas against N. fowleri, the IC50 values were: 71.85, 73.95, and 63.01 mu g.mL-1, respectively. Additionally, nanoformulations significantly reduced N. fowleri-mediated host cell death, while nanoformulations along with fluconazole and metronidazole considerably reduced Balamuthia-mediated human cell damage. Finally, all the tested drugs and their nanoformulations revealed limited cytotoxic activity against human cerebral microvascular endothelial cell (HBEC-5i) cells. Conclusion These compounds should be developed into novel chemotherapeutic options for use against these distressing infections due to free-living amoebae, as currently there are no effective treatments.Öğe Bacterial flora varies throughout the saltwater crocodile (Crocodylus porosus) gastrointestinal tract(Amer Veterinary Medical Assoc, 2023) Siddiqui, Ruqaiyyah; Maciver, Sutherland K.; Anuar, Tengku Shahrul; Khan, Naveed AhmedOBJECTIVEThe objective of this study was to determine bacterial flora throughout the gastrointestinal tract of a saltwater crocodile (Crocodylus porosus) using 16S rRNA gene analysis.ANIMALSA 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.PROCEDURESThree 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 prim- ers (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.RESULTSThe 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 intes- tine 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 RELEVANCEFor 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.Öğe Brain-eating Amoebae, Nasal Cleansing, and Water Quality Monitoring Programmes(Springer, 2023) Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed[Abstract Not Available]Öğe Can Acanthamoeba Harbor Monkeypox Virus?(Mdpi, 2023) Siddiqui, Ruqaiyyah; Muhammad, Jibran Sualeh; Alharbi, Ahmad M.; Alfahemi, Hasan; Khan, Naveed AhmedAcanthamoeba is well known to host a variety of microorganisms such as viruses, bacteria, protozoa, and yeast. Given the recent number of cases of monkeypox infection, we speculate that amoebae may be aiding viral transmission to the susceptible hosts. Although there is no confirmatory evidence to suggest that Acanthamoeba is a host to monkeypox (a double-stranded DNA virus), the recent discovery of mimivirus (another double-stranded DNA virus) from Acanthamoeba, suggests that amoebae may shelter monkeypox virus. Furthermore, given the possible spread of monkeypox virus from animals to humans during an earlier outbreak, which came about after patients came in contact with prairie dogs, it is likely that animals may also act as mixing vessel between ubiquitously distributed Acanthamoeba and monkeypox virus, in addition to the environmental habitat that acts as an interface in complex interactions between diverse microorganisms and the host.Öğe Can Amphotericin B-mediated effects be limited using intranasal versus intravenous route?(Newlands Press Ltd, 2023) Siddiqui, Ruqaiyyah; Ong, Timothy Yu Yee; Maciver, Sutherland; Khan, Naveed AhmedAim: 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. Plain language summary: Brain infections due to parasites are often fatal. One of the reasons is the inability of drugs to get to the brain. When given in large dose to reach the brain, the drug can cause serious side effects. Here, we tested the side effects of Amphotericin B (drug of choice against brain-eating amoebae), when given intranasally versus intravenous. Our findings clearly show that intranasal route limits the side effects of Amphotericin B. These are important findings and should serve as an important step in the development of effective therapy against parasitic infections affecting the brain. Tweetable abstract: Targeting brain-eating amoebae: Amphotericin B-mediated host tissue toxicity can be limited when given intranasally. [GRAPHICS.]Öğe Cardiovascular changes under the microgravity environment and the gut microbiome(Elsevier, 2024) Siddiqui, Ruqaiyyah; Qaisar, Rizwan; Al-Dahash, Khulood; Altelly, Ahmad Hashem; Elmoselhi, Adel B.; Khan, Naveed AhmedIn view of the critical role the gut microbiome plays in human health, it has become clear that astronauts' gut microbiota composition changes after spending time in space. Astronauts are exposed to several risks in space, including a protracted period of microgravity, radiation, and mechanical unloading of the body. Several deleterious effects of such an environment are reported, including orthostatic intolerance, cardiovascular endothelial dysfunction, cellular and molecular changes, and changes in the composition of the gut microbiome. Herein, the correlation between the gut microbiome and cardiovascular disease in a microgravity environment is evaluated. Additionally, the relationship between orthostatic hypotension, cardiac shrinkage and arrhythmias during spaceflight, and cellular alterations during spaceflight is reviewed. Given its impact on human health in general, modifying the gut microbiota may significantly promote astronaut health and performance. This is merited, given the prospect of augmented human activities in future space missions.Öğe Cell death of Acanthamoeba castellanii following exposure to antimicrobial agents commonly included in contact lens disinfecting solutions(Springer, 2024) Thomas, Louise; Khan, Naveed Ahmed; Siddiqui, Ruqaiyyah; Alawfi, Bader S.; Lloyd, DavidSeveral antimicrobial agents are commonly included in contact lens disinfectant solutions including chlorhexidine diacetate (CHX), polyhexamethylene biguanide (PHMB) or myristamidopropyl dimethylamine (MAPD); however, their mode of action, i.e. necrosis versus apoptosis is incompletely understood. Here, we determined whether a mechanism of cell death resembling that of apoptosis was present in Acanthamoeba castellanii of the T4 genotype (NEFF) following exposure to the aforementioned antimicrobials using the anticoagulant annexin V that undergoes rapid high affinity binding to phosphatidylserine in the presence of calcium, making it a sensitive probe for phosphatidylserine exposure. The results revealed that under the conditions employed in this study, an apoptotic pathway of cell death in this organism at the tested conditions does not occur. Our findings suggest that necrosis is the likely mode of action; however, future mechanistic studies should be accomplished in additional experimental conditions to further comprehend the molecular mechanisms of cell death in Acanthamoeba.Öğe Cinnamic acid and lactobionic acid based nanoformulations as a potential antiamoebic therapeutics(Academic Press Inc Elsevier Science, 2023) Akbar, Noor; Kawish, Muhammad; Jabri, Tooba; Khan, Naveed Ahmed; Shah, Muhammad Raza; Siddiqui, RuqaiyyahAcanthamoeba castellanii causes granulomatous amoebic encephalitis, an uncommon but severe brain infection and sight-threatening Acanthamoeba keratitis. Most of the currently used anti-amoebic treatments are not always effective, due to persistence of the cyst stage, and recurrence can occur. Here in this study we synthesize cin-namic acid and lactobionic acid-based magnetic nanoparticles (MNPs) using co-precipitation technique. These nanoformulations were characterized by Fourier transform infrared spectroscopy and Atomic form microscopy. The drugs alone (Hesperidin, Curcumin and Amphotericin B), magnetic NPs alone, and drug-loaded nano -for-mulations were evaluated at a concentration of 100 mu g/mL for antiamoebic activity against a clinical isolate of A. castellanii. Amoebicidal assays revealed that drugs and conjugation of drugs and NPs further enhanced amoebicidal effects of drug-loaded nanoformulations. Drugs and drug-loaded nanoformulations inhibited both encystation and excystation of amoebae. In addition, drugs and drug-loaded nanoformulations inhibited parasite binding capability to the host cells. Neither drugs nor drug-loaded nanoformulations showed cytotoxic effects against host cells and considerably reduced parasite-mediated host cell death. Overall, these findings imply that conjugation of medically approved drugs with MNPs produce potent anti-Acanthamoebic effects, which could eventually lead to the development of therapeutic medications.Öğe Cockroaches: a potential source of novel bioactive molecule(s) for the benefit of human health(SPRINGER, 2022) Siddiqui, Ruqaiyyah; Yara Elmashak; Khan, Naveed AhmedCockroaches are one of the hardiest insects that have survived on this planet for millions of years. They thrive in unhygienic environments, are able to survive without food for up to 30 days, without air for around 45 min and being submerged under water for 30 min. Cockroaches are omnivorous and feed on a variety of foods, including cellulose and plastic, to name a few. It is intriguing that cockroaches are able to endure and flourish under conditions that are harmful to Homo sapiens. Given the importance of the gut microbiome on its' host physiology, we postulate that the cockroach gut microbiome and/or its metabolites, may be contributing to their "hardiness", which should be utilized for the discovery of biologically active molecules for the benefit of human health. Herein, we discuss the biology, diet/habitat of cockroaches, composition of gut microbiome, cellular senescence, and resistance to infectious diseases and cancer. Furthermore, current knowledge of the genome and epigenome of these remarkable species is considered. Being one of the most successful and diverse insects, as well as their extensive use in traditional and Chinese medicine, the lysates/extracts and gut microbial metabolites of cockroaches may offer a worthy resource for novel bioactive molecule(s) of therapeutic potential for the benefit of human health and may be potentially used as probiotics.
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