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1.
In Silico Pharmacol ; 12(1): 17, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525049

RESUMO

Neisseria gonorrhea is a sexually transmitted disease from gonorrhea that lacks treatment; despite the urgency, the absence of adequate drugs, lack of human correlates of protection, and inadequate animal models of infection have delayed progress toward the prevention of gonococcal infection. Lactobacillus crispatus is a lactic acid bacterium typically found in the human vaginal microbiota. Peptides from L. crispatus have shown a potential therapeutic option for targetting N. gonorrhea. Bioinformatics analysis is important for speeding up drug target acquisition, screening refinement, and evaluating adverse effects and drug resistance prediction. Therefore, this study identified an antimicrobial peptide from the bacteriocin immunity protein (BIP) of L. crispatus using the bioinformatics tool and Collection of Antimicrobial Peptide (CAMPR3). Based on the AMP score and highest ADMET properties, the peptide SM20 was chosen for docking analysis. SM20 was docked against multiple proteins from the genome of the AMR bacterium N. gonorrhea using an online tool; protein-peptide interactions were established and visualized using the PyMol visualizing tool. Molecular docking was carried out using the CABSdock tool, and multiple conformations were obtained against the membrane proteins of N. gonorrhoea. The peptide SM20 exhibited higher docking scores and ADMET properties. Therefore, SM20 could be further encapsulated with cellulose; it can be applied topically to the genital tract to target N. gonorrhea infection. The controlled release of the antimicrobial peptide from the gel can provide sustained delivery of the treatment, increasing its efficacy and reducing the risk of resistance development.

2.
Acta Parasitol ; 69(1): 734-746, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38411855

RESUMO

INTRODUCTION: Argulus spp. infestation is a significant challenge for aquaculture, currently, there are no approved medications available to efficiently manage this parasite. Consequently, mechanical removal of parasites using forceps and natural substances like herbs are being explored as alternative treatment methods. Pellitorine (PLE) is a naturally occurring compound found in several plant species. It is classified as an alkaloid and belongs to the class of compounds known as amides. MATERIALS AND METHODS: This study aimed to evaluate the effectiveness of PLE in preventing Argulus spp. infestations in goldfish (Carassius auratus) and to determine the optimal dosage of PLE for the detachment of Argulus spp. RESULTS: The findings of this study revealed that PLE enhanced the immune response of goldfish by promoting superoxide dismutase (SOD) and catalase (CAT) in Argulus-infected goldfish. Additionally, PLE induces reactive oxygen species (ROS) generation and cellular damage in the Argulus. PLE at a dosage of 5 mg/mL was able to detach 80% of the argulus from goldfish within 12 h. Therapeutic index was found to be 5.99, suggesting that PLE is the safest drug. CONCLUSIONS: Therefore, our findings suggest that PLE can be a suitable and effective treatment option for preventing Argulus infestations in goldfish. The results of this study can guide the use of PLE at an optimal dosage to control Argulus infestation in goldfish.


Assuntos
Antioxidantes , Antiparasitários , Arguloida , Ácidos Graxos Insaturados , Doenças dos Peixes , Carpa Dourada , Animais , Carpa Dourada/parasitologia , Arguloida/efeitos dos fármacos , Doenças dos Peixes/parasitologia , Doenças dos Peixes/tratamento farmacológico , Antioxidantes/farmacologia , Antiparasitários/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Catalase/metabolismo , Superóxido Dismutase/metabolismo
3.
Reprod Toxicol ; 124: 108531, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38176575

RESUMO

Male infertility is a multifactorial condition influenced by epigenetic regulation, oxidative stress, and mitochondrial dysfunction. Oxidative stress-induced damage leads to epigenetic modifications, disrupting gene expression crucial for spermatogenesis and fertilization. Paternal exposure to oxidative stress induces transgenerational epigenetic alterations, potentially impacting male fertility in offspring. Mitochondrial dysfunction impairs sperm function, while leukocytospermia exacerbates oxidative stress-related sperm dysfunction. Therefore, this review focuses on understanding these mechanisms as vital for developing preventive strategies, including targeting oxidative stress-induced epigenetic changes and implementing lifestyle modifications to prevent male infertility. This study investigates how oxidative stress affects the epigenome and sperm production, function, and fertilization. Unravelling the molecular pathways provides valuable insights that can advance our scientific understanding. Additionally, these findings have clinical implications and can help to address the significant global health issue of male infertility.


Assuntos
Infertilidade Masculina , Doenças Mitocondriais , Masculino , Humanos , Epigênese Genética , Sêmen , Espermatozoides/metabolismo , Infertilidade Masculina/genética , Infertilidade Masculina/metabolismo , Estresse Oxidativo , Doenças Mitocondriais/genética , Doenças Mitocondriais/metabolismo
4.
Microb Pathog ; 184: 106387, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37821050

RESUMO

Bacteria communicate with each other through contact-dependent and contact-independent mechanisms. While certain contact-dependent mechanisms, such as Type IV and Type VI, have received considerable attention, nanotubes-mediated communication among gut bacteria remains largely unknown. The purpose of this study is to demonstrate the presence of nanotube production in both gut commensal and gut pathogenic bacteria. And also aims to show how Enterococcus faecalis utilizes nanotubes to combat Salmonella ser. Typhi (S. Typhi), a pathogen in the gut. The research findings suggest that the formation of nanotubes is an inherent trait observed in both Gram-positive and Gram-negative bacteria. Interestingly, bacteria generate nanotubes in dynamic environments, biofilms, and even within the gut of zebrafish. These nanotubes develops over time in accordance with the duration of incubation. Furthermore, E. faecalis effectively combats S. Typhi through mechanisms that depend on physical contact rather than indirect methods. Notably, E. faecalis protects zebrafish larvae from S. Typhi infections by reducing reactive oxygen species and cell death, and concurrently boosting the production of antioxidant enzymes. It is hypothesized that E. faecalis might eliminate S. Typhi by transferring toxic metabolites into the pathogen via nanotubes. Gene expression analysis highlights that proinflammatory markers such as TNF-α, IL-1ß, and IL-6 are elevated in Salmonella-infected larvae. However, co-treatment with E. faecalis counters this effect. Findings of this study underscores the significance of nanotubes as a vital machinery for bacterial communication and distribution of virulence factors. Exploring nanotubes-mediated communication at a molecular level could pave the way for innovative therapeutic interventions.


Assuntos
Enterococcus faecalis , Peixe-Zebra , Animais , Bactérias , Enterococcus faecalis/metabolismo , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Salmonella typhi
5.
Artigo em Inglês | MEDLINE | ID: mdl-36889534

RESUMO

Aluminium (Al) is proven to be a potent environmental neurotoxin involved in progressive neurodegeneration. Al primarily induces oxidative stress by free radical generation in the brain, followed by neuronal apoptosis. Antioxidants are promising therapeutic options for Al toxicity. Piperlongumine is traditionally long known for its medicinal properties. Therefore, the present study has been designed to explore the antioxidant role of trihydroxy piperlongumine (THPL) against Al-induced neurotoxicity in the zebrafish model. Zebrafish exposed to AlCl3 exhibited higher oxidative stress and altered locomotion. Adult fish displayed anxiety comorbid with depression phenotype. THPL increases antioxidant enzyme activity by quenching Al-induced free radicals and lipid peroxidation, thus minimizing oxidative damage in the brain. THPL rescues behavior deficits and improves anxiety-like phenotype in adult fish. Histological alterations caused by Al were also attenuated on administration with THPL. Results of the study demonstrate the neuroprotective role of THPL against Al-induced oxidative damage and anxiety, which could be exploited as a psychopharmacological drug.


Assuntos
Alumínio , Antioxidantes , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Alumínio/toxicidade , Cloreto de Alumínio , Peixe-Zebra/metabolismo , Compostos de Alumínio/toxicidade , Cloretos/toxicidade , Estresse Oxidativo
6.
Biomed Mater Eng ; 26(1-2): 89-96, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26484559

RESUMO

The wear of the bearing surfaces of total disc replacement (TDR) is a key problem leads to reduction in the lifetime of the prosthesis and it mainly occurs due to the range of clearances of the articulating surface between the superior plate and core. The objective of this paper is to estimate the wear using finite element concepts considering the different radial clearances between the articulating surfaces of ceramic on ceramic type Lumbar Total Disc Replacement (LTDR). The finite element (FE) model was subjected to wear testing protocols according to loading profile of International Standards Organization (ISO) 18192 standards through 10 million cycles. The radial clearance value of 0.05 mm showed less volumetric wear when compared with other radial clearance values. Hence, low radial clearance values are suitable for LTDR to minimize the wear.


Assuntos
Cerâmica/química , Desenho Assistido por Computador , Vértebras Lombares/cirurgia , Modelos Teóricos , Substituição Total de Disco/instrumentação , Simulação por Computador , Análise de Falha de Equipamento , Análise de Elementos Finitos , Fricção , Humanos , Desenho de Prótese , Estresse Mecânico
7.
J Ethnopharmacol ; 142(1): 283-6, 2012 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-22543169

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The roots are reportedly used to treat diarrhoea, dysentery, leprosy, skin diseases and fever. AIM OF STUDY: The aim of present study was to investigate the in vitro antimicrobial potential of ethanol extract of Trichdesma indicum root, and its purified compounds and to validate scientifically its use in traditional medicine. MATERIAL AND METHODS: The root of Trichdesma indicum was extracted with ethanol and subjected to chromatographic separation for isolation of phytochemical compounds. Structures of isolated compounds were elucidated by spectroscopic methods. The antimicrobial activities of the ethanol extract of T. indicum and isolated compounds were primarily evaluated by a disc diffusion test. The anti-microbial efficacy of the ethanol extract or isolated compounds was then assessed in vitro by determining minimal inhibition concentration (MIC) and minimal bactericidal or fungicidal concentration (MBC/MFC). RESULTS: n-Decanyl laurate (1), n-tetradecanyl laurate (2), n-nonacosanyl palmitate (3), stigmast-5-en-3ß-ol-21(24)-olide (4), n-pentacos-9-one (5), n-dotriacont-9-one-13-ene (6), stigmast-5-en-3ß-ol-23-one (7) and lanast-5-en-3ß-D-glucopyranosyl-21 (24)-olide (8) were isolated from ethanol extract of T.indicum. The ethanol extract and isolated compounds (1-8) showed varying degrees of antimicrobial activities. The ethanol extract exhibited potent growth inhibitory activity against S. aureus, B. subtilis and C. albicans with an MIC value of 19.2 µg/ml. Among all the isolated compounds, lanast-5-en-3ß-D-glucopyranosyl-21 (24)-olide (8) displayed strongest antibacterial activity against S. aureus with MIC value of 2.4 µg/ml. CONCLUSIONS: The results of present study provide ground basis for the potential use of the ethanol extract Trichodesma indicum root as well as the some of the isolated compounds in the treatment of infections associated with the studied microorganisms.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Boraginaceae , Extratos Vegetais/farmacologia , Bactérias/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Etanol/química , Testes de Sensibilidade Microbiana , Raízes de Plantas/química
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