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1.
R Soc Open Sci ; 11(4): 231755, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38633350

RESUMO

This study focuses on the development of antimicrobial fibres for use in medical and healthcare textile industries. Carbon dots (CDs) were designed with boronic acid groups for the attachment to cellulose fibres found in cotton textiles and to enhance their attachment to glycogens on bacterial surfaces. Boronic acid-based and curcumin-based CDs were prepared and characterized using various techniques, showing a nanoscale size and zeta potential values. The CDs inhibited the growth of both Staphylococcus epidermidis and Escherichia coli bacteria, with UV-activated CDs demonstrating improved antibacterial activity. The antimicrobial activity of the CDs was then tested, revealing strong adherence to cellulose paper fibres with no CD diffusion and potent inhibition of bacterial growth. Cytotoxicity assays on human cell lines showed no toxicity towards cells at concentrations of up to 100 µg ml-1 but exhibited increased toxicity at concentrations exceeding 1000 µg ml-1. However, CD-modified cellulose paper fibres showed no toxicity against human cell lines, highlighting the antimicrobial properties of the CD-modified cellulose fibres are safe for human use. These findings show promising potential for applications in both industrial and clinical settings.

2.
Eur J Med Chem ; 271: 116440, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38678825

RESUMO

Antimicrobial and chemotherapy resistance are escalating medical problem of paramount importance. Yet, research for novel antimicrobial and anticancer agents remains lagging behind. With their reported medical applications, DNA minor groove binders (MGBs) are worthy of exploration. In this study, the approach of structure-based drug design was implemented to generate 11 MGB compounds including a novel class of bioactive alkyne-linked MGBs. The NCI screening protocol was utilized to evaluate the antitumor activity of the target MGBs. Furthermore, a variety of bactericidal, cytopathogenicity, MIC90, and cytotoxicity assays were carried out using these MGBs against 6 medically relevant bacteria: Salmonella enterica, Escherichia coli, Serratia marcescens, Bacillus cereus, Streptococcus pneumoniae and Streptococcus pyogenes. Moreover, molecular docking, molecular dynamic simulations, DNA melting, and isothermal titration calorimetry (ITC) analyses were utilized to explore the binding mode and interactions between the most potent MGBs and the DNA duplex d(CGACTAGTCG)2. NCI results showed that alkyne-linked MGBs (26 & 28) displayed the most significant growth inhibition among the NCI-60 panel. In addition, compounds MGB3, MGB4, MGB28, and MGB32 showed significant bactericidal effects, inhibited B. cereus and S. enterica-mediated cytopathogenicity, and exhibited low cytotoxicity. MGB28 and MGB32 demonstrated significant inhibition of S. pyogenes, whereas MGB28 notably inhibited S. marcescens and all four minor groove binders significantly inhibited B. cereus. The ability of these compounds to bind with DNA and distort its groove dimensions provides the molecular basis for the allosteric perturbation of proteins-DNA interactions by MGBs. This study shed light on the mechanism of action of MGBs and revealed the important structural features for their antitumor and antibacterial activities, which are important to guide future development of MGB derivatives as novel antibacterial and anticancer agents.


Assuntos
Antibacterianos , Antineoplásicos , DNA , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Humanos , Relação Estrutura-Atividade , DNA/química , DNA/metabolismo , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular
3.
J Egypt Public Health Assoc ; 98(1): 21, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38110669

RESUMO

A notable decrease in conventional cigarette smoking has been witnessed on a global scale. However, this decrease has been accompanied by an equally striking global increase in the consumption of alternative tobacco products (ATPs), namely e-cigarettes and midwakh in the Arabian Gulf region. A literature review was used to outline the chemical composition of these two ATPs and review their impacts on health. The study was conducted using databases like PubMed, Google Scholar, MDPI, and WorldCat. The literature search included terms such as "e-cigarettes," "midwakh," "dokha," "heath impacts," "psychological effects," "social influences," and "cigarette smoking" with emphasis on literature from the Arabian Gulf region. Data shows that midwakh contains markedly high levels of tar, nicotine, and various compounds of notable effects on the human body. Similarly, it was found that e-cigarettes contain non-negligible amounts of nicotine and other chemical compounds that may not have been extensively investigated. Alarming reports of system-specific effects brought about by midwakh, and e-cigarette consumption, have been reported, although further research is needed to deduce the mechanism. We also discussed some of the social and psychological factors leading to their consumption within this population. Hence, this review raises questions around the safety of these two types of ATPs and encourages comprehensive studies globally and regionally.

4.
Antibiotics (Basel) ; 12(5)2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37237778

RESUMO

All currently approved antibiotics are being met by some degree of resistance by the bacteria they target. Biofilm formation is one of the crucial enablers of bacterial resistance, making it an important bacterial process to target for overcoming antibiotic resistance. Accordingly, several drug delivery systems that target biofilm formation have been developed. One of these systems is based on lipid-based nanocarriers (liposomes), which have shown strong efficacy against biofilms of bacterial pathogens. Liposomes come in various types, namely conventional (charged or neutral), stimuli-responsive, deformable, targeted, and stealth. This paper reviews studies employing liposomal formulations against biofilms of medically salient gram-negative and gram-positive bacterial species reported recently. When it comes to gram-negative species, liposomal formulations of various types were reported to be efficacious against Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, and members of the genera Klebsiella, Salmonella, Aeromonas, Serratia, Porphyromonas, and Prevotella. A range of liposomal formulations were also effective against gram-positive biofilms, including mostly biofilms of Staphylococcal strains, namely Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus saprophyticus subspecies bovis, followed by Streptococcal strains (pneumonia, oralis, and mutans), Cutibacterium acnes, Bacillus subtilis, Mycobacterium avium, Mycobacterium avium subsp. hominissuis, Mycobacterium abscessus, and Listeria monocytogenes biofilms. This review outlines the benefits and limitations of using liposomal formulations as means to combat different multidrug-resistant bacteria, urging the investigation of the effects of bacterial gram-stain on liposomal efficiency and the inclusion of pathogenic bacterial strains previously unstudied.

5.
Antibiotics (Basel) ; 12(4)2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37107117

RESUMO

The 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 µg/mL against S. enteric, and MIC90 at 6.2 µg/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.

6.
Cont Lens Anterior Eye ; 46(2): 101758, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36243521

RESUMO

PURPOSE: This aim of this study was to assess anti-parasitic properties of deep eutectic solvents against eye pathogen, Acanthamoeba, often associated with the use of contact lens. METHODS: Assays were performed to investigate the effects of various Methyltrioctylammonium chloride-based deep eutectic solvents on Acanthamoeba castellanii, comprising amoebicidal assays, encystment assays, excystment assays, cytotoxicity assays by measuring lactate dehydrogenase release from human cells, and cytopathogenicity assays to determine parasite-mediated host cell death. RESULTS: In a 2 h incubation period, DES-B, DES-C, DES-D, and DES-E exhibited up to 85 % amoebicidal activity at micromolar doses, which was enhanced further following 24 h incubation. When tested in encystment assays, selected deep eutectic solvents abolished cyst formation and were able to block excystment of A. castellanii. All solvents exhibited minimal human cell cytotoxicity except DES-D. Finally, all tested deep eutectic solvents inhibited amoeba-mediated cytopathogenicity, except DES-B. CONCLUSIONS: Deep eutectic solvents show potent antiamoebic effects. These findings are promising and could lead to the development of novel contact lens disinfectants, as well as opening several avenues to explore the molecular mechanisms, various doses and incubation periods, and use of different bases against Acanthamoeba castellanii.


Assuntos
Acanthamoeba castellanii , Amebicidas , Humanos , Solventes Eutéticos Profundos , Amebicidas/farmacologia , Compostos de Amônio Quaternário/farmacologia , Soluções para Lentes de Contato/farmacologia
7.
Antibiotics (Basel) ; 11(12)2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36551378

RESUMO

Acanthamoeba 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 ß-cyclodextrin, and tested them against A. castellanii via amoebicidal, amoebistatic, encystment, excystment, cytopathogenicity, and cytotoxicity assays at a concentration of 100 µg/mL. Notably, zinc oxide ß-cyclodextrin ceftriaxone significantly inhibited A. castellanii growth and cytopathogenicity. Additionally, both zinc oxide ß-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.

8.
Biology (Basel) ; 11(11)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36421397

RESUMO

The possession of two X chromosomes may come with the risk of various illnesses, females are more likely to be affected by osteoarthritis, heart disease, and anxiety. Given the reported correlations between gut microbiome dysbiosis and various illnesses, the female gut microbiome is worthy of exploration. Herein, we discuss the composition of the female gut microbiota and its dysbiosis in pathologies affecting the female population. Using PubMed, we performed a literature search, using key terms, namely: "gut microbiome", "estrogen", "menopause", "polycystic ovarian syndrome", "pregnancy", and "menstruation". In polycystic ovarian syndrome (PCOS), the abundance of Bacteroides vulgatus, Firmicutes, Streptococcus, and the ratio of Escherichia/Shigella was found to be increased while that of Tenericutes ML615J-28, Tenericutes 124-7, Akkermansia, Ruminococcaceae, and Bacteroidetes S24-7 was reduced. In breast cancer, the abundance of Clostridiales was enhanced, while in cervical cancer, Prevotella, Porphyromonas, and Dialister were enhanced but Bacteroides, Alistipes, and members of Lachnospiracea, were decreased. In ovarian cancer, Prevotella abundance was increased. Interestingly, the administration of Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus reuteri, and Lactobacillus fermentum ameliorated PCOS symptoms while that of a mix of Bifidobacterium lactis W51, Bifidobacterium bifidum W23, Lactobacillus brevis W63, Bifidobacterium lactis W52, Lactobacillus salivarius W24, Lactobacillus acidophilus W37, Lactococcus lactis W19, Lactobacillus casei W56, and Lactococcus lactis W58 alleviated vascular malfunction and arterial stiffness in obese postmenopausal women, and finally, while further research is needed, Prevotella maybe protective against postmenopausal bone mass loss. As several studies report the therapeutic potential of probiotics and since the gut microbiota of certain female pathological states has been relatively characterized, we speculate that the administration of certain bacterial species as probiotics is warranted, as novel independent or adjunct therapies for various female pathologies.

9.
Mol Biochem Parasitol ; 250: 111493, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35753525

RESUMO

Acanthamoeba castellanii is a protist pathogen that can cause sight-threatening keratitis and a fatal infection of the central nervous system, known as granulomatous amoebic encephalitis. In this study, effects of five malonic acid and salicylic acid-based deep eutectic solvents (DES) on A. castellanii were investigated. These are salicylic acid-trioctylphosphine (DES 1), salicylic acid- trihexylamine (DES 2), salicylic acid-trioctylamine (DES 3), malonic acid-trioctylphosphine (DES 4) and malonic acid-trihexylamine (DES 5). The experiments were done by performing amoebicidal, encystment, excystment, cytopathogenicity, and cytotoxicity assays. At micromolar dosage, the solvents DES 2 and DES 3 displayed significant amoebicidal effects (P < 0.05), inhibited encystment and excystment, undermined the cell-mediated cytopathogenicity of A. castellanii, and also displayed minimal cytotoxicity to human cells. Conversely, the chemical components of these solvents: salicylic acid, trihexylamine, and trioctylamine showed minimal effects when tested individually. These results are very promising and to the best of our knowledge, are reported for the first time on the effects of deep eutectic solvents on amoebae. These results can be applied in the development of new formulations of novel contact lens disinfectants against Acanthamoeba castellanii.


Assuntos
Ceratite por Acanthamoeba , Acanthamoeba castellanii , Amebicidas , Lentes de Contato , Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/prevenção & controle , Amebicidas/química , Amebicidas/farmacologia , Amebicidas/uso terapêutico , Soluções para Lentes de Contato/farmacologia , Soluções para Lentes de Contato/uso terapêutico , Solventes Eutéticos Profundos , Humanos , Ácido Salicílico/farmacologia , Ácido Salicílico/uso terapêutico
10.
Folia Microbiol (Praha) ; 67(6): 825-835, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35711021

RESUMO

Acne is a frequently presented dermatological condition brought about by an interplay among inflammation, increased sebum production, hyperkeratinisation, and predominantly Propionibacterium acnes (renamed as Cutibacterium acnes) proliferation, leading to debilitating psychological scars. However, it has been shown that it is the loss of microbial diversity in the skin and the imbalance among C. acnes phylotypes that brings about acne rather than the C. acnes species as a whole. Interestingly, recent evidence suggests that other microorganisms may be implicated, such as the fungi Malassezia and the bacteria Cutibacterium granulosum. A plethora of scientific evidence suggests that the gut microbiome is implicated in the overall health and physiology of the host; studies show that the gut microbiome of acne patients is distinct and depicts less microbial diversity compared to individuals without acne. Herein, using the key terms: acne, C. acnes, IGF-1, sebum, and gut microbiome, we carried out a review of the literature, using Google Scholar and PubMed, and discussed the role of the gut and skin microbiome in relation to acne, as a narrative review. The role of hormones, diet, sebum, and stress in relation to the gut microbiome was also investigated. Therapeutic implications and the use of pre-/postbiotics are also deliberated upon. In this light, future research should investigate the relationship between the gut microbiome and the agreed upon factors of acne pathology, potentially leading to the discovery of novel acne treatments with milder side effects.


Assuntos
Acne Vulgar , Microbioma Gastrointestinal , Microbiota , Humanos , Acne Vulgar/tratamento farmacológico , Acne Vulgar/microbiologia , Propionibacterium acnes/fisiologia , Pele/microbiologia
11.
J Eukaryot Microbiol ; 68(5): e12857, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33987951

RESUMO

Vermamoeba vermiformis are one of the most prevalent free-living amoebae. These amoebae are ubiquitous and also thermotolerant. Of concern, V. vermiformis have been found in hospital water networks. Furthermore, associations between V. vermiformis and pathogenic bacteria have been reported, such as Legionella pneumophila. Moreover, V. vermiformis are well known to host viruses, bacteria, and other microorganisms and cases of keratitis due to V. vermiformis in conjunction with other amoebae have been reported. Despite the preceding, the medical importance of V. vermiformis is still an ongoing discussion and its genome has been only recently sequenced. Herein, we present a review of the current understanding of the biology and pathogenesis pertaining to V. vermiformis, as well as its' role as an etiological agent and trojan horse. An approach known as theranostics which combines both diagnosis and therapy could be utilized to eradicate and diagnose keratitis cases caused by such amoebae. Given the rise in global warming, it is imperative to investigate these rarely studied amoebae and to understand their importance in human health.


Assuntos
Amoeba , Lobosea , Bactérias , Água , Microbiologia da Água
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