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1.
Environ Toxicol Pharmacol ; 109: 104479, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38821154

RESUMO

Plant growth regulators (PGRs) are increasingly used to promote sustainable agriculture, but their unregulated use raises concerns about potential environmental risks. Indole-3-acetic acid (IAA), a commonly used PGR, has been the subject of research on its developmental toxicity in the in-vivo zebrafish model. IAA exposure to zebrafish embryos caused oxidative stress, lipid peroxidation, and cellular apoptosis. The study also revealed that critical antioxidant genes including sod, cat, and bcl2 were downregulated, while pro-apoptotic genes such as bax and p53 were upregulated. IAA exposure also hampered normal cardiogenesis by downregulating myl7, amhc, and vmhc genes and potentially influencing zebrafish neurobehavior. The accumulation of IAA was confirmed by HPLC analysis of IAA-exposed zebrafish tissues. These findings underscore the need for further study on the potential ecological consequences of IAA use and the need for sustainable agricultural practices.

2.
Toxicol Appl Pharmacol ; 486: 116917, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38555004

RESUMO

Indole-3-acetic acid (IAA) is the most widely utilized plant growth regulator. Despite its extensive usage, IAA is often overlooked as an environmental pollutant. Due to its protein-binding nature, it also functions as a uremic toxin, contributing to its association with chronic kidney disease (CKD). While in vitro and epidemiological research have demonstrated this association, the precise impact of IAA on cardiovascular disease in animal models is unknown. The main objective of this study is to conduct a mechanistic analysis of the cardiotoxic effects caused by IAA using male Wistar albino rats as the experimental model. Three different concentrations of IAA (125, 250, 500 mg/kg) were administered for 28 days. The circulating IAA concentration mimicked previously observed levels in CKD patients. The administration of IAA led to a notable augmentation in heart size and heart-to-body weight ratio, indicating cardiac hypertrophy. Echocardiographic assessments supported these observations, revealing myocardial thickening. Biochemical and gene expression analyses further corroborated the cardiotoxic effects of IAA. Dyslipidemia, increased serum c-Troponin-I levels, decreased SOD and CAT levels, and elevated lipid peroxidation in cardiac tissue were identified. Moreover, increased expression of cardiac inflammatory biomarkers, including ANP, BNP, ß-MHC, Col-III, TNF-α, and NF-κB, was also found in the IAA-treated animals. Histopathological analysis confirmed the cardiotoxic nature of IAA, providing additional evidence of its adverse effects on cardiovascular health. These results offer insights into the potential negative impact of IAA on cardiovascular function, and elucidating the underlying mechanisms of its cardiotoxicity.


Assuntos
Cardiomegalia , Ácidos Indolacéticos , Ratos Wistar , Animais , Masculino , Ratos , Cardiomegalia/induzido quimicamente , Cardiomegalia/patologia , Estresse Oxidativo/efeitos dos fármacos , Miocárdio/metabolismo , Miocárdio/patologia , Biomarcadores/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Cardiotoxicidade
3.
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
4.
J Microbiol ; 62(2): 75-89, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38383881

RESUMO

The emergence of carbapenem-resistant Pseudomonas aeruginosa, a multi-drug-resistant bacteria, is becoming a serious public health concern. This bacterium infects immunocompromised patients and has a high fatality rate. Both naturally and synthetically produced chalcones are known to have a wide array of biological activities. The antibacterial properties of synthetically produced chalcone were studied against P. aeruginosa. In vitro, study of the compound (chalcone derivative named DKO1), also known as (2E)-1-(5-methylfuran-2-yl)-3-(4-nitrophenyl) prop-2-en-1-one, had substantial antibacterial and biofilm disruptive action. DKO1 effectively shielded against P. aeruginosa-induced inflammation, oxidative stress, lipid peroxidation, and apoptosis in zebrafish larvae. In adult zebrafish, the treatment enhanced the chances of survivability and reduced the sickness-like behaviors. Gene expression, biochemical analysis, and histopathology studies found that proinflammatory cytokines (TNF-α, IL-1ß, IL-6, iNOS) were down regulated; antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) levels increased, and histoarchitecture was restored in zebrafish. The data indicate that DKO1 is an effective antibacterial agent against P. aeruginosa demonstrated both in vitro and in vivo.


Assuntos
Chalcona , Chalconas , Adulto , Animais , Humanos , Peixe-Zebra , Pseudomonas aeruginosa/metabolismo , Chalcona/metabolismo , Chalcona/farmacologia , Chalconas/metabolismo , Chalconas/farmacologia , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Bactérias , Testes de Sensibilidade Microbiana
5.
Mol Neurobiol ; 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191695

RESUMO

Aluminium (AL) is a strong environmental neurotoxin linked to neurodegenerative disorders. Widespread industrial use leads to its presence in water systems, causing bioaccumulation in organisms. This, in turn, results in the bioaccumulation of AL in various organisms. Several studies have highlighted the benefits of enhanced physical activity in combating neurodegenerative diseases. Meanwhile widespread presence of apigenin in aquatic environment has been largely overlooked, in terms of its potential to counter AL-induced neurotoxicity. The combined impact of exercise and apigenin in mitigating the effects of AL-induced neurotoxicity in aquatic animals remains unexplored. Hence, the objective of this study is to determine whether the combined treatment of exercise and apigenin can effectively alleviate the chronic neurotoxicity induced by AL. Zebrafish that were exposed to AL showed behaviours resembling anxiety, increased aggression, unusual swimming pattern, and memory impairment, which are typical features observed in Alzheimer's disease (AD)-like syndrome. Combined treatment of exercise and apigenin protects zebrafish from AL-induced neurotoxicity, which was measured by improvements in memory, reduced anxiety and aggression, and increased levels of antioxidant enzymes and acetylcholinesterase (AChE) activity. Furthermore, AL exposure is associated with increased expression of genes related to neuroinflammation and AD. However, synergistic effect of exercise and apigenin counteract this effect in AL-treated zebrafish. These findings suggest that AL is involved in neurodegenerative diseases in fish, which could affect the integrity of aquatic ecosystem. Hence, there is a strong correlation between enhanced physical activity, apigenin, and the well-being of the ecosystem.

6.
Environ Pollut ; 338: 122686, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37802289

RESUMO

Environmental pollution is inherently linked to several metabolic diseases and high mortality. The kidney is more susceptible to environmental pollutants compared to other organs as it is involved in concentrating and filtering most of these toxins. Few epidemiological studies revealed the intrinsic relationship between exposure to Endocrine Disrupting Chemicals (EDCs) and CKD development. Though EDCs have the potential to cause severe pathologies, the specific molecular mechanisms by which they accelerate the progression of CKD remain elusive. In particular, our understanding of how pollutants affect the progression of chronic kidney disease (CKD) through the gut-kidney axis is currently limited. EDCs modulate the composition and function of the gut microbial community and favor the colonization of harmful gut pathogens. This alteration leads to an overproduction of uremic toxin and membrane vesicles. These vesicles carry several inflammatory molecules that exacerbate inflammation and renal tissue damage and aggravate the progression of CKD. Several experimental studies have revealed potential pathways by which uremic toxin further aggravates CKD. These include the induction of membrane vesicle production in host cells, which can trigger inflammatory pathways and insulin resistance. Reciprocally, CKD can also modulate gut bacterial composition that might further aggravate CKD condition. Thus, EDCs pose a significant threat to kidney health and the global CKD burden. Understanding this complicated issue necessitates multidisciplinary initiatives such as strict environmental controls, public awareness, and the development of novel therapeutic strategies targeting EDCs.


Assuntos
Disruptores Endócrinos , Insuficiência Renal Crônica , Toxinas Biológicas , Humanos , Disruptores Endócrinos/toxicidade , Toxinas Urêmicas , Insuficiência Renal Crônica/induzido quimicamente , Rim/metabolismo , Inflamação
7.
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
8.
Sci Total Environ ; 902: 165988, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37549705

RESUMO

Microplastics (MP), tiny plastic particles, can be ingested by fish through their habitat or contaminated food sources. When combined with a high-fat diet (HFD), MP exposure may lead to increased MP accumulation in fish and negative impacts on their health. However, the underlying mechanisms of how MP and HFD interact to promote fat accumulation in fish remain poorly understood. In this study, we aimed to evaluate the combined effect of HFD and polyethylene MP (PE-MP) in the zebrafish model (Danio rerio) and decipher its molecular mechanisms. Adult zebrafish exposed to the combined HFD and PE-MP showed elevated lipid accumulation, total cholesterol, triglycerides, and abnormal swimming behavior compared to HFD-fed fish. Histological and gene expression analysis revealed severe hepatic inflammation and injury, resembling nonalcoholic fatty liver disease (NAFLD) in the HFD + PE-MP exposed zebrafish. Moreover, HFD and PE-MP exposure upregulated genes related to lipogenesis (SREBP1, FAS, and C/EBPα) and inflammation (tnfα, il1ß, and il-6) in the liver. These findings underscore the interactive effect of environmental pollutants and fish diet, emphasizing the importance of improving fish culture practices to safeguard fish health and human consumers from microplastic contamination through the food chain. This research sheds light on the complex interactions between microplastics and diet, providing valuable insights into the potential risks of microplastic pollution in aquatic ecosystems and the implications for human health. Understanding the underlying molecular mechanisms will contribute to international research efforts to mitigate the adverse effects of microplastics on both environmental and public health.


Assuntos
Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica , Animais , Adulto , Humanos , Microplásticos/toxicidade , Microplásticos/metabolismo , Peixe-Zebra/metabolismo , Plásticos/metabolismo , Polietileno/toxicidade , Polietileno/metabolismo , Dieta Hiperlipídica/efeitos adversos , Larva/metabolismo , Ecossistema , Fígado/metabolismo , Inflamação/patologia
9.
Pharmacol Res ; 194: 106856, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37460001

RESUMO

Diverse microbial communities colonize different habitats of the human body, including gut, oral cavity, nasal cavity and tissues. These microbial communities are known as human microbiome, plays a vital role in maintaining the health. However, changes in the composition and functions of human microbiome can result in chronic low-grade inflammation, which can damage the epithelial cells and allows pathogens and their toxic metabolites to translocate into other organs such as the liver, heart, and kidneys, causing metabolic inflammation. This dysbiosis of human microbiome has been directly linked to the onset of several non-communicable diseases. Recent metabolomics studies have revealed that pathogens produce several uraemic toxins. These metabolites can serve as inter-kingdom signals, entering the circulatory system and altering host metabolism, thereby aggravating a variety of diseases. Interestingly, Enterobacteriaceae, a critical member of Proteobacteria, has been commonly associated with several non-communicable diseases, and the abundance of this family has been positively correlated with uraemic toxin production. Hence, this review provides a comprehensive overview of Enterobacterial translocation and their metabolites role in non-communicable diseases. This understanding may lead to the identification of novel biomarkers for each metabolic disease as well as the development of novel therapeutic drugs.


Assuntos
Microbioma Gastrointestinal , Microbiota , Doenças não Transmissíveis , Humanos , Enterobacteriaceae , Inflamação/microbiologia
10.
Microb Pathog ; 180: 106123, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37088400

RESUMO

Pseudomonas aeruginosa (PA) is an opportunistic pathogen that causes healthcare-associated infection and high mortality in immunocompromised patients. It produces several virulence factors through quorum sensing (QS) mechanisms that is essential for subverting host immune system. Even front-line antibiotics are unable to control PA pathogenicity due to the emergence of antibiotic resistance. Luteolin is a naturally derived compound that has proven to be the effective drug to annihilate pathogens through quorum quenching mechanism. In this study, the protective effect of luteolin against the PA-mediated inflammation was demonstrated using zebrafish model. Luteolin protects zebrafish from PA infection and increases their survival rate. It was found that PA-mediated ROS, lipid peroxidation, and apoptosis were also significantly reduced in luteolin-treated zebrafish larvae. Open field test (OFT) reveals that luteolin rescued PA-infected zebrafish from retarded swimming behavior. Furthermore, luteolin increases SOD and CAT levels and decreases LDH and NO levels in PA-infected zebrafish compare to control group. Histological and gene expression analysis reveals that luteolin protects PA-infected zebrafish by decreasing gut inflammation and altering the expression of inflammatory (TNF-α, IL-1ß, IL-6) and antioxidant markers (iNOS, SOD, CAT). Thus, luteolin was found to have dual effect in protecting PA-infected zebrafish by decreasing virulence factors production in PA and stimulating host immune system. This is the first study demonstrating the protective effect of luteolin using animal model. Hence, luteolin could be used as a future therapeutic drug to control multi-drug resistant PA.


Assuntos
Infecções por Pseudomonas , Fatores de Virulência , Animais , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Pseudomonas aeruginosa , Luteolina/farmacologia , Peixe-Zebra , Percepção de Quorum , Inflamação , Superóxido Dismutase/metabolismo , Antibacterianos/metabolismo , Biofilmes , Proteínas de Bactérias/metabolismo , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/patologia
11.
Appl Biochem Biotechnol ; 195(8): 4851-4863, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37079270

RESUMO

Obesity is linked to the development of major metabolic disorders such as type 2 diabetes, cardiovascular disease, and cancer. Recent research has focused on the molecular link between obesity and oxidative stress. Obesity impairs antioxidant function, resulting in dramatically increased reactive oxygen levels and apoptosis. In this study, we investigated the effect of IW13 peptide on inhibiting lipid accumulation and regulating the antioxidant mechanism to normalize the lipid metabolism in HFD induced zebrafish larvae. Our results showed that co-treatment with IW13 peptide showed a protective effect in HFD zebra fish larvae by increasing the survival and heart rate. However, IW13 peptide co-treatment reduced triglycerides and cholesterol levels while also restoring the SOD and CAT antioxidant enzymes. In addition, IW13 co-treatment inhibited the formation of lipid peroxidation and superoxide anion by regulating the glutathione level. Also, the results showed that IW13 specifically downregulated the expression of the lipogenic-specific genes (C/EBP-α, SREBP1, and FAS). The findings exhibited that the IW13 peptide with effective antioxidant and anti-obesity activity could act as a futuristic drug to treat obesity and oxidative stress-related diseases.


Assuntos
Diabetes Mellitus Tipo 2 , Metabolismo dos Lipídeos , Animais , Peixe-Zebra/metabolismo , Antioxidantes/metabolismo , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína alfa Estimuladora de Ligação a CCAAT/farmacologia , Proteína alfa Estimuladora de Ligação a CCAAT/uso terapêutico , Estresse Oxidativo , Obesidade/metabolismo , Transdução de Sinais , Proteínas Quinases/metabolismo , Treonina/metabolismo , Treonina/farmacologia , Treonina/uso terapêutico , Serina/metabolismo , Serina/farmacologia , Serina/uso terapêutico
12.
Exp Gerontol ; 173: 112088, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36646294

RESUMO

Ageing is a complex process that is associated with changes in the composition and functions of gut microbiota. Reduction of gut commensals is the hallmarks of ageing, which favours the expansion of pathogens even in healthy centenarians. Interestingly, gut Enterobacteriaceae have been found to be increased with age and also consistently observed in the patients with metabolic diseases. Thus, they are associated with all-cause mortality, regardless of genetic origin, lifestyle, and fatality rate. Moreover, Enterobacteriaceae are also implicated in accelerating the ageing process through telomere attrition, cellular senescence, inflammasome activation and impairing the functions of mitochondria. However, acceleration of ageing is likely to be determined by intrinsic interactions between Enterobacteriaceae and other associated gut bacteria. Several studies suggested that Enterobacteriaceae possess genes for the synthesis of uraemic toxins. In addition to intestine, Enterobacteriaceae and their toxic metabolites have also been found in other organs, such as adipose tissue and liver and that are implicated in multiorgan dysfunction and age-related diseases. Therefore, targeting Enterobacteriaceae is a nuance approach for reducing inflammaging and enhancing the longevity of older people. This review is intended to highlight the current knowledge of Enterobacteriaceae-mediated acceleration of ageing process.


Assuntos
Enterobacteriaceae , Toxinas Urêmicas , Idoso de 80 Anos ou mais , Humanos , Idoso , Envelhecimento/fisiologia , Longevidade/fisiologia , Fígado
13.
Phytother Res ; 37(4): 1449-1461, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36450691

RESUMO

Polycystic ovarian syndrome (PCOS) is a hormonal disorder that causes enlargement of ovaries and follicular maturation arrest, which lacks efficient treatment. N2, a semi-natural triterpenoid from the neem family, was already reported to have antioxidant and antiinflammatory properties in our previous report. This study investigated the anti-androgenic property of N2 on testosterone-induced oxidative stress in Chinese Hamster Ovarian cells (CHO) and PCOS zebrafish model. The testosterone exposure disrupted the antioxidant enzymes and ROS level and enhanced the apoptosis in both CHO cells and PCOS zebrafish. However, N2 significantly protected the CHO cells from ROS and apoptosis. N2 improved the Gonado somatic index (GSI) and upregulated the expression of the SOD enzyme in zebrafish ovaries. Moreover, the testosterone-induced follicular maturation arrest was normalized by N2 treatment in histopathology studies. In addition, the gene expression studies of Tox3 and Denndla in zebrafish demonstrated that N2 could impair PCOS condition. Furthermore, to confirm the N2 activity, the in-silico studies were performed against PCOS susceptible genes Tox3 and Dennd1a using molecular docking and molecular dynamic simulations. The results suggested that N2 alleviated the oxidative stress and apoptosis in-vitro and in-vivo and altered the expression of PCOS key genes.


Assuntos
Síndrome do Ovário Policístico , Feminino , Humanos , Animais , Cricetinae , Síndrome do Ovário Policístico/patologia , Cricetulus , Peixe-Zebra/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/metabolismo , Células CHO , Simulação de Acoplamento Molecular , Transdução de Sinais , Testosterona , Estresse Oxidativo , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Proteínas Adaptadoras de Sinalização de Receptores de Domínio de Morte/genética , Proteínas Adaptadoras de Sinalização de Receptores de Domínio de Morte/metabolismo
14.
Front Microbiol ; 13: 943278, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36177463

RESUMO

Cell-to-cell communication is a fundamental process of bacteria to exert communal behaviors. Sputum samples of patients with cystic fibrosis have often been observed with extensive mycobacterial genetic diversity. The emergence of heterogenic mycobacterial populations is observed due to subtle changes in their morphology, gene expression level, and distributive conjugal transfer (DCT). Since each subgroup of mycobacteria has different hetero-resistance, they are refractory against several antibiotics. Such genetically diverse mycobacteria have to communicate with each other to subvert the host immune system. However, it is still a mystery how such heterogeneous strains exhibit synchronous behaviors for the production of quorum sensing (QS) traits, such as biofilms, siderophores, and virulence proteins. Mycobacteria are characterized by division of labor, where distinct sub-clonal populations contribute to the production of QS traits while exchanging complimentary products at the community level. Thus, active mycobacterial cells ensure the persistence of other heterogenic clonal populations through cooperative behaviors. Additionally, mycobacteria are likely to establish communication with neighboring cells in a contact-independent manner through QS signals. Hence, this review is intended to discuss our current knowledge of mycobacterial communication. Understanding mycobacterial communication could provide a promising opportunity to develop drugs to target key pathways of mycobacteria.

15.
Brain Res ; 1788: 147941, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35550141

RESUMO

Acrylamide is a thermal process contaminant, which gets global attention due to its neurotoxic nature and its omnipresence in carbohydrate-rich foods. Chronic exposure to acrylamide leads to neuronal deterioration and motor dysfunction. Acrylamide could severely affect the antioxidant defense system, especially in the developing brain leading to premature neurological disorders. Acrylamide forms adduct in presynaptic neurons leading to neuroinflammation which is also a factor to consider. In this present study, we have explored whether our benzo[b]thiophene analogs, 1-(3-hydroxybenzo[b]thiophen-2-yl) ethanone (BP) and 1-(3-hydroxybenzo[b]thiophen-2-yl) propan-1-one hydrate (EP) with antioxidant activity, could inhibit the acrylamide-induced neurotoxicity-like behavior in zebrafish larvae. The experiment was set up to expose 3 days post fertilized (dpf) larvae to acrylamide (0.75 mM) for 3 days with or without compounds (80 µM). Locomotion behavioral analysis, antioxidants, glutathione, and acetylcholineesterase activity in the head region were analyzed after one day of the experimental procedure. We witnessed a restoration effect on glutathione redox dynamics. Since glutathione plays a crucial role in the detoxification of acrylamide, it is necessary to maintain the glutathione redox cycle to eliminate acrylamide from the body. BP and EP reduced the pro-inflammatory transcript in the head, which correlates with the reduction in oxidative stress. Finally, BP and EP showed a positive effect on synaptic vesicle cycling transcript and partially restores the motor neuron response to stimuli. Findings in this study showed the ability of compound BP and EP possess therapeutic value in oxidative stress-associated neurological disorders.


Assuntos
Acrilamida , Síndromes Neurotóxicas , Acrilamida/toxicidade , Animais , Antioxidantes/metabolismo , Glutationa/metabolismo , Larva , Síndromes Neurotóxicas/tratamento farmacológico , Oxirredução , Estresse Oxidativo , Tiofenos/farmacologia , Peixe-Zebra/metabolismo
16.
Microb Pathog ; 166: 105542, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35439554

RESUMO

Pseudomonas aeruginosa (PA) is an opportunistic pathogen that causes high mortality in cystic fibrosis patients. Treatment failures often occur due to the emergence of antibiotic resistance. Inhibition of virulence factors production without suppressing the growth of the pathogens is a potential alternative strategy to control the antibiotic resistance. In order to accomplish, three different interaction studies were performed using Bacillus subtilis BR4, PA and their extracellular contents. Firstly, co-cultivation was performed with different cell density of BR4 or PA. In co-culture setup (F), high cell density of BR4 significantly inhibits the biofilm formation of PA in a growth-independent manner (p < 0.01). To substantiate the biofilm inhibition, LC-MS/MS was performed and metabolic profile of monocultures and cocultures were compared. Multivariate analysis corroborated that metabolic profile of coculture setup (F) is drastically different from other coculture and monoculture setups. To check the effect of extracellular content of PA on BR4, supernatant of PA was extracted with ethyl acetate and different concentration of that extract (PA-EXT) was supplemented with BR4 culture. Exogenous supplementation PA-EXT (40 µg/mL) led to increased biofilm inhibitory activity (p < 0.01) in BR4. Further, to check the effect of extracellular content of BR4, PA was grown in the supernatant of BR4. PA survives in the spent media of BR4 without biofilm formation. Though 50% spent media of BR4 was replaced with fresh media, PA could not produce biofilm. In support of this, LC-MS/MS analysis has revealed that abundance of quorum sensing (QS) signals was reduced in the spent media grown PA than control. Furthermore, BR4 protects zebrafish larvae (Danio rerio) against PA infection and increases their survival rate (p < 0.05). We found that PA-induced oxidative stress and apoptosis were also significantly reduced in the BR4-pretreated larval group than control group. These results clearly indicate that BR4 exerts growth-independent QS inhibition in PA, suggesting that it could be used as a probiotic for future therapeutic interventions.


Assuntos
Probióticos , Pseudomonas aeruginosa , Animais , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Bacillus subtilis/metabolismo , Biofilmes , Cromatografia Líquida , Humanos , Metabolômica , Percepção de Quorum , Espectrometria de Massas em Tandem , Fatores de Virulência/metabolismo , Peixe-Zebra
17.
J Basic Microbiol ; 62(7): 801-814, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35355286

RESUMO

Cell-to-cell communication is essentially required in bacteria for the production of multiple virulence factors and successful colonization in the host. Targeting the virulence factors production without hampering the growth of the pathogens is a potential strategy to control pathogenesis. To accomplish this, a total of 43 mangrove isolates were screened for quorum quenching (QQ) activity against Pseudomonas aeruginosa (PA), in which eight bacteria have shown antibiofilm activity without hampering the growth of the PA. Prominent QQ activity was observed in Bacillus subtilis BR4. Previously, we found that BR4 produces stigmatellin Y, a structural analogue of PQS signal of PA, which could competitively bind with PqsR receptor and inhibits the quorum sensing (QS) system of PA. Further, stigmatellin Y containing ethyl acetate extract (S-EAE) (100 µg ml-1 ) of BR4 significantly inhibits (p < 0.001) the biofilm formation of PA. Confocal laser scanning microscope (CLSM) and scanning electron microscope (SEM) analysis also fortified the QQ activity of BR4. Furthermore, S-EAE of BR4 (500 µg ml-1 ) has significantly reduced the production of virulence factors, including protease, elastase, pyocyanin and extracellular polysaccharides substances. Furthermore, liquid chromatography-mass spectrometry (LC-MS)/MS analysis affirms that BR4 intercepts the PQS-mediated QS system by reducing the synthesis of as many PQS signals, including precursor molecule (243.162313 Da) of PQS signal. Thus, S-EAE of B. subtilis BR4 could be used as a promising therapeutic agent to combat QS system-mediated pathogenesis of PA. Further therapeutic potentials of stigmatellin Y to be evaluated in clinical studies for the treatment of multidrug resistant PA.


Assuntos
Pseudomonas aeruginosa , Percepção de Quorum , Bacillus subtilis/metabolismo , Proteínas de Bactérias/metabolismo , Biofilmes , Polienos , Pseudomonas aeruginosa/metabolismo , Fatores de Virulência
18.
Front Cardiovasc Med ; 8: 737505, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631835

RESUMO

There has been a huge increase in diabetes and its associated cardiovascular complications over the last decade, predominantly in the middle- and low-income countries. In these countries, the majority live in rural areas. The Rural Epidemiology of Diabetes in South India (REDSI) study was aimed to analyze the prevalence of diabetes, cardiovascular risk factors, and its complications in rural farming and non-farming villages in Tamil Nadu, South India. A research survey on the prevalence of self-reported diabetes, cardiovascular risk factors (age, sex, obesity, hypertension, hypercholesterolemia, alcohol and tobacco use) and agricultural occupational exposure was executed among 106,111 people from 61 villages in the state of Tamil Nadu, South India, during 2015-2018. Overall, we observed a diabetes prevalence of 11.9% in rural South India. A nearly two-fold higher prevalence of diabetes was observed among the farming community (15.0%) compared to that among the non-farming population (8.7%). Logistic regression analyses revealed a strong association with agrochemical exposure (P < 0.0001) and diabetes prevalence among rural farming people. Our survey indicates a high prevalence of diabetes in rural South India particularly among the farming community. This survey in conjunction with other epidemiological and experimental studies raises the need for understanding the etiology of diabetes and other cardiovascular risk factors in rural communities.

19.
Gut Microbes ; 13(1): 1959841, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34455923

RESUMO

Complex inter-bacterial interactions largely influence the structure and function of the gut microbial community. Though several host-associated phenomena have often been shown to be involved in the stability, structure, and function of the gut microbial community, the implication of contact-dependent and contact-independent inter-bacterial interactions has been overlooked. Such interactions are tightly governed at multiple layers through several extracellular organelles, including contact-dependent inhibition (CDI), nanotubes, type VI secretion system (T6SS), and membrane vesicles (MVs). Recent advancements in molecular techniques have revealed that such extracellular organelles function beyond exhibiting competitive behavior and are also involved in manifesting cooperative behaviors. Cooperation between bacteria occurs through the sharing of several beneficial molecules including nucleic acids, proteins, metabolites, and nutrients among the members of the community, while competition occurs by means of multiple toxins. Intrinsic coordination between contact-dependent and contact-independent mechanisms collectively provides a fitness advantage and increased colonization resistance to the gut microbiota, where molecular trafficking plays a key role. This review is intended to provide a comprehensive view of the salient features of the different bacterial interactions and to highlight how microbiota deploy multifaceted organelles, for exerting both cooperative and competitive behaviors. We discuss the current knowledge of bacterial molecular trafficking and its impact on shaping the gut microbial community.


Assuntos
Bactérias/metabolismo , Microbioma Gastrointestinal/fisiologia , Organelas/fisiologia , Percepção de Quorum/fisiologia , Transdução de Sinais/fisiologia , Bactérias/classificação , Bactérias/genética , Inibição de Contato/fisiologia , Interações Microbianas/fisiologia , Nanotubos , Sistemas de Secreção Tipo VI/fisiologia
20.
Probiotics Antimicrob Proteins ; 11(1): 186-197, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29181803

RESUMO

The bioprospecting proficient of novel pigmented probiotic strains with respect to aquaculture industry was unexplored hitherto. In this study, we investigated the probiotic potential of novel pigmented bacterial strains isolated from the indigenous soil sediments in their vicinal habitats, which were screened for their antimicrobial activity against aquatic pathogens using agar well diffusion assay. The strains namely Exiguobacterium acetylicum (S01), Aeromonas veronii (V03), and Chryseobacterium joostei (V04) were phenotypically identified and confirmed by 16S rRNA gene sequence analysis. Further characterization revealed that strains S01 and V03 survive relatively in lower pH and higher bile salt concentrations and possess good adherence ability and broad-spectrum antibiotic susceptibility. The isolate S01 exhibited the higher adhesion ability to hydrocarbons (82%) and mannose-specific adhesion (msa) gene expression. Additionally, the probiotic effects were evaluated in Artemia nauplii fed with algae supplemented with S01, V03, and V04 strains (2.7 × 107 cfu/mL) for 3 days under axenic environment. We observed a significant increase (p < 0.05) in the survival rate of Artemia nauplii treated with S01 (83 ± 5%) and V03 (55 ± 5%), whereas the survival rate was only 30 ± 0% in the untreated group. Moreover, the individual length (IL) was increased in treated group S01 (156.7 ± 2.2 µm), V03 (146.1 ± 3.4 µm), and V04 (134.4 ± 2.5 µm) compared with untreated group (116.0 ± 4.8 µm). Our results revealed that E. acetylicum S01 exhibits desirable functional probiotic attributes compared to A. veronii and C. joostei and it would be a promising probiotic strain, which can be efficiently used in the aquaculture applications.


Assuntos
Aeromonas/fisiologia , Aquicultura , Bacillaceae/fisiologia , Chryseobacterium/fisiologia , Probióticos/farmacologia , Microbiologia do Solo , Aeromonas/isolamento & purificação , Bacillaceae/isolamento & purificação , Aderência Bacteriana , Chryseobacterium/isolamento & purificação
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