Yazar "Boghossian, Anania" seçeneğine göre listele

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    Anti-Balamuthia mandrillaris and anti-Naegleria fowleri effects of drugs conjugated with various nanostructures
    (Springer, 2023) Siddiqui, Ruqaiyyah; Boghossian, Anania; Alqassim, Saif S.; Kawish, Muhammad; Gul, Jasra; Jabri, Tooba; Shah, Muhammad Raza
    Balamuthia mandrillaris and Naegleria fowleri are protist pathogens that can cause fatal infections. Despite mortality rate of > 90%, there is no effective therapy. Treatment remains problematic involving repurposed drugs, e.g., azoles, amphotericin B and miltefosine but requires early diagnosis. In addition to drug discovery, modifying existing drugs using nanotechnology offers promise in the development of therapeutic interventions against these parasitic infections. Herein, various drugs conjugated with nanoparticles were developed and evaluated for their antiprotozoal activities. Characterizations of the drugs' formulations were accomplished utilizing Fourier-transform infrared spectroscopy, efficiency of drug entrapment, polydispersity index, zeta potential, size, and surface morphology. The nanoconjugates were tested against human cells to determine their toxicity in vitro. The majority of drug nanoconjugates exhibited amoebicidal effects against B. mandrillaris and N. fowleri. Amphotericin B-, Sulfamethoxazole-, Metronidazole-based nanoconjugates are of interest since they exhibited significant amoebicidal effects against both parasites (p < 0.05). Furthermore, Sulfamethoxazole and Naproxen significantly diminished host cell death caused by B. mandrillaris by up to 70% (p < 0.05), while Amphotericin B-, Sulfamethoxazole-, Metronidazole-based drug nanoconjugates showed the highest reduction in host cell death caused by N. fowleri by up to 80%. When tested alone, all of the drug nanoconjugates tested in this study showed limited toxic effects against human cells in vitro (less than 20%). Although these are promising findings, prospective work is warranted to comprehend the mechanistic details of nanoconjugates versus amoebae as well as their in vivo testing, to develop antimicrobials against the devastating infections caused by these parasites.
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    Imidazothiazole derivatives exhibited potent effects against brain-eating amoebae
    (MDPI, 2022) Siddiqui, Ruqaiyyah; El-Gamal, Mohammed, I; Boghossian, Anania; Saeed, Balsam Qubais; Oh, Chang-Hyun; Abdel-Maksoud, Mohammed S.; Alharbi, Ahmad M.; Alfahemi, Hasan; Khan, Naveed Ahmed
    Naegleria fowleri (N. fowleri) is a free-living, unicellular, opportunistic protist responsible for the fatal central nervous system infection, primary amoebic meningoencephalitis (PAM). Given the increase in temperatures due to global warming and climate change, it is estimated that the cases of PAM are on the rise. However, there is a current lack of awareness and effective drugs, meaning there is an urgent need to develop new therapeutic drugs. In this study, the target compounds were synthesized and tested for their anti-amoebic properties against N. fowleri. Most compounds exhibited significant amoebicidal effects against N. fowleri; for example, 1h, 1j, and 1q reduced N. fowleri's viability to 15.14%, 17.45% and 28.78%, respectively. Furthermore, the majority of the compounds showed reductions in amoeba-mediated host death. Of interest are the compounds 1f, 1k, and 1v, as they were capable of reducing the amoeba-mediated host cell death to 52.3%, 51%, and 56.9% from 100%, respectively. Additionally, these compounds exhibit amoebicidal properties as well; they were found to decrease N. fowleri's viability to 26.41%, 27.39%, and 24.13% from 100%, respectively. Moreover, the MIC50 values for 1e, 1f, and 1h were determined to be 48.45 mu M, 60.87 mu M, and 50.96 mu M, respectively. Additionally, the majority of compounds were found to exhibit limited cytotoxicity, except for 1l, 1o, 1p, 1m, 1c, 1b, 1zb, 1z, 1y, and 1x, which exhibited negligible toxicity. It is anticipated that these compounds may be developed further as effective treatments against these devastating infections due to brain-eating amoebae.
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    The increasing importance of the oral microbiome in periodontal health and disease
    (Future Sci Ltd, 2023) Siddiqui, Ruqaiyyah; Badran, Zahi; Boghossian, Anania; Alharbi, Ahmad M.; Alfahemi, Hasan; Khan, Naveed Ahmed
    Plain language summaryThis paper discusses what we currently know about the microbiome and periodontal diseases. Plaque buildup can happen for various reasons, like eating sugary foods, changes in saliva and the microorganisms in the mouth and gut. To treat periodontal diseases, we currently use antimicrobial medications and scaling. For patients with periodontitis, root planing and deep pocket debridement are used. Dental probiotics are getting attention as a potential treatment option. They work by competing with harmful bacteria for nutrients and surfaces in the mouth, and there are also probiotics that target the gut microbiome. Herein, the aim is to discuss the current knowledge of microbiome and periodontal diseases. Current treatment strategies include mechanical therapy such as root planing, scaling, deep pocket debridement and antimicrobial chemotherapy as an adjuvant therapy. Among promising therapeutic strategies, dental probiotics and oral microbiome transplantation have gained attention, and may be used to treat bacterial imbalances by competing with pathogenic bacteria for nutrients and adhesion surfaces, as well as probiotics targeting the gut microbiome. Development of strategies to prevent and treat periodontal diseases are warranted as both are highly prevalent and can affect human health. Further studies are necessary to better comprehend the microbiome in order to develop innovative preventative measures as well as efficacious therapies against periodontal diseases. Tweetable abstractThe microbiome plays a critical in periodontal health and disease, and thus should be targeted in dental therapies.
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    Nanocarrier Drug Conjugates Exhibit Potent Anti-Naegleria fowleri and Anti-Balamuthia mandrillaris Properties
    (Mdpi, 2023) Siddiqui, Ruqaiyyah; Boghossian, Anania; Kawish, Muhammad; Jabri, Tooba; Shah, Muhammad Raza; Anuar, Tengku Shahrul; Al-Shareef, Zainab
    Given the opportunity and access, pathogenic protists (Balamuthia mandrillaris and Naegleria fowleri) can produce fatal infections involving the central nervous system. In the absence of effective treatments, there is a need to either develop new antimicrobials or enhance the efficacy of existing compounds. Nanocarriers as drug delivery systems are gaining increasing attention in the treatment of parasitic infections. In this study, novel nanocarriers conjugated with amphotericin B and curcumin were evaluated for anti-amoebic efficacy against B. mandrillaris and N. fowleri. The results showed that nanocarrier conjugated amphotericin B exhibited enhanced cidal properties against both amoebae tested compared with the drug alone. Similarly, nanocarrier conjugated curcumin exhibited up to 75% cidal effects versus approx. 50% cidal effects for curcumin alone. Cytopathogenicity assays revealed that the pre-treatment of both parasites with nanoformulated-drugs reduced parasite-mediated host cellular death compared with the drugs alone. Importantly, the cytotoxic effects of amphotericin B on human cells alone were reduced when conjugated with nanocarriers. These are promising findings and further suggest the need to explore nanocarriers as a means to deliver medicine against parasitic infections.
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    The pivotal role of the gut microbiome in colorectal cancer
    (MDPI, 2022) Siddiqui, Ruqaiyyah; Boghossian, Anania; Alharbi, Ahmad M; Alfahemi, Hasan; Khan, Naveed Ahmed
    Colorectal cancer is the third most diagnosed cancer worldwide and the second most prevalent cause of cancer-related mortality. It is believed that alterations within the gut microbiome may impact the development and progression of cancer. Additionally, the diet an individual maintains and the amount of alcohol consumed can alter the microbiome, thus impacting the development of colorectal cancer. A diet focused on fiber intake is considered beneficial, as it contains short-chain fatty acids such as butyrate, which have antitumor properties. Furthermore, current treatment strategies, such as chemotherapy, have various side effects. In this review, we discuss the role of the gut microbiome and oral bacteria in relation to colorectal cancer. We also deliberate on the role of diet and alcohol consumption in the development of colorectal cancer. Moreover, the influence of the various metabolites within the gut and the importance of gut inflammation in the development of colorectal cancer are explained. Finally, potential therapies such as fecal microbiota transfer and post/prebiotics are elaborated on. To further comprehend risk factors in the development of colorectal cancer, future studies are warranted to determine the precise mechanisms of action between the gut microbiome and carcinogenesis in order to develop therapies that may target gut microbial dysbiosis.