scholarly journals Exploring the cytotoxic mechanisms of Pediocin PA-1 towards HeLa and HT29 cells by comparison to known bacteriocins: Microcin E492, enterocin heterodimer and Divercin V41

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0251951
Author(s):  
George P. Buss ◽  
Cornelia M. Wilson
Keyword(s):  
Bioinformatic Analysis ◽  
3D Modelling ◽  
Future Research ◽  
Toll Like Receptor ◽  
Sequence Alignments ◽  
Toll Like Receptor 4 ◽  
Dual Effect ◽  
Ht29 Cells ◽  
The Difference

The purpose of this study was to explore potential mechanisms of cytotoxicity towards HeLa and HT29 cells displayed by Pediocin PA-1. We did this by carrying out sequence alignments and 3D modelling of related bacteriocins which have been studied in greater detail: Microcin E492, Enterocin AB heterodimer and Divercin V41. Microcin E492 interacts with Toll-Like Receptor 4 in order to activate an apoptosis reaction, sequence alignment showed a high homology between Pediocin PA-1 and Microcin E492 whereas 3D modelling showed Pediocin PA-1 interacting with TLR-4 in a way reminiscent of Microcin E492. Furthermore, Pediocin PA-1 had the highest homology with the Enterocin heterodimer, particularly chain A; Enterocin has also shown to cause an apoptotic response in cancer cells. Based on this we are led to strongly believe Pediocin PA-1 interacts with TLRs in order to cause cell death. If this is the case, it would explain the difference in cytotoxicity towards HeLa over HT29 cells, due to difference in expression of particular TLRs. Overall, we believe Pediocin PA-1 exhibits a dual effect which is dose dependant, like that of Microcin. Unfortunately, due to the COVID-19 pandemic, we were unable to carry out experiments in the lab, and the unavailability of important data meant we were unable to provide and validate out solid conclusions, but rather suggestions. However, bioinformatic analysis is still able to provide information regarding structure and sequence analysis to draw plausible and evidence based conclusions. We have been able to highlight interesting findings and how these could be translated into future research and therapeutics in order to improve the quality of treatment and life of cancer patients.

scholarly journals Exploring the cytotoxic mechanisms of Pediocin PA-1 towards HeLa and HT29 cells by comparison to known bacteriocins: Microcin E492, Enterocin Heterodimer and Divercin V41.

2021 ◽  
Author(s):  
George Paul Buss ◽  
Cornelia Wilson
Keyword(s):  
3D Modelling ◽  
Future Research ◽  
Toll Like Receptor ◽  
Reaction Sequence ◽  
Sequence Alignments ◽  
Toll Like Receptor 4 ◽  
Dual Effect ◽  
Ht29 Cells ◽  
The Difference

The purpose of this study was to explore potential mechanisms of cytotoxicity towards HeLa and HT29 cells displayed by Pediocin PA-1. We did this by carrying out sequence alignments and 3D modelling of related bacteriocins which have been studied in greater detail: Microcin E492, Eneterocin AB heterodimer and Divercin V41. Microcin E492 interacts with Toll-Like Receptor 4 in order to activate an apoptosis reaction, sequence alignment showed a high homology between Pediocin PA-1 and Microcin E492 and 3D modelling showed Pediocin PA-1 interacting with TLR-4 in a way reminiscent of Microcin E492. Furthermore, Pediocin PA-1 had the highest homology with the Enterocin heterodimer, particularly chain A; Enterocin has also shown to cause an apoptotic response in cancer cells. Based on this we are led to strongly believe Pediocin PA-1 interacts with TLRs in order to cause cell death. If this is the case it would explain the difference in cytotoxicity towards HeLa over HT29 cells, due to difference in expression of particular TLRs. Overall, we believe Pediocin PA-1 exhibits a dual effect which is dose dependant, like that of Microcin. Unfortunately, the COVID-19 pandemic meant that we were unable to carry out experiments in the lab, and the unavailability of important data meant we were unable to make solid conclusions but rather suggestions. However despite this we have still been able to highlight interesting findings and how these could be translated into future research and therapeutics in order to improve the quality of treatment and life of cancer patients.

scholarly journals Association between Toll-Like Receptor 4 and Occurrence of Type 2 Diabetes Mellitus Susceptible to Pulmonary Tuberculosis in Northeast China

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Yuze Li ◽  
Dianzhong Li ◽  
Jinfeng Zhang ◽  
Shurui Liu ◽  
Haijun Chen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Pulmonary Tuberculosis ◽  
Gene Polymorphism ◽  
Future Research ◽  
Control Group ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4

The purpose of this study is to explore why type 2 diabetes mellitus (T2DM) patients are susceptible to pulmonary tuberculosis through detection of serum Toll-like receptor 4 (TLR4), an important immune-related receptor, especially in terms of content and TLR4gene polymorphism. Patients with T2DM complicated by pulmonary tuberculosis (T2DMTB) were selected as the case group and T2DM patients without tuberculosis were selected as the control group. Forty patients in each group were randomly selected and their serum TLR4levels were detected and compared. Determination of six sites of TLR4gene polymorphism was carried out in 238 T2DMTB patients and 310 patients with T2DM, and results showed that the serum TLR4content of the T2DMTB group was significantly lower than that of the T2DM group (p<0.05). The six sites of TLR4gene polymorphism did not show significant associations with T2DMTB risk. No statistically significant differences in genotype distributions were observed between T2DMTB patients and patients with T2DM when studied using the recessive and dominant genetic models. How two diseases with contradictory nutritional statuses can occur in the same person is difficult to explain from environmental factors perspective alone. Future research should study the causes of T2DMTB from the perspective of genetics.

scholarly journals Manipulating the microbiome alters regenerative outcomes in Xenopus laevis tadpoles vis lipopolysaccharide signalling

2021 ◽  
Author(s):  
Phoebe A Chapman ◽  
Campbell B Gilbert ◽  
Thomas J Devine ◽  
Daniel T Hudson ◽  
Joanna Ward ◽  
...  
Keyword(s):  
Xenopus Laevis ◽  
Skin Microbiome ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tail Regeneration ◽  
Rrna Sequencing ◽  
Bacterial Lipopolysaccharides ◽  
Tadpole Skin ◽  
Editing Level

Xenopus laevis tadpoles can regenerate functional tails, containing spinal cord, notochord, muscle, fin, blood vessels and nerves, except for a brief refractory period at around one week of age. At this stage, amputation of the tadpole's tail may either result in scarless wound healing, or the activation of a regeneration programme, which replaces the lost tissues. We recently demonstrated a link between bacterial lipopolysaccharides and successful tail regeneration in refractory stage tadpoles, and proposed that this could result from lipopolysaccharides binding to Toll-like receptor 4 (TLR4). Here, we have used 16S rRNA sequencing to show that the tadpole skin microbiome is highly variable between sibships and that the community can be altered by raising embryos in the antibiotic gentamicin. Six gram-negative genera, including Delftia and Chryseobacterium, were over-represented in tadpoles that underwent tail regeneration. Lipopolysaccharides purified from a commensal Chryseobacterium spp. XDS4, an exogenous Delftia spp. or Escherichia coli could significantly increase the number of antibiotic-raised tadpoles that attempted regeneration. Conversely, the quality of regeneration was impaired in native-raised tadpoles exposed to the antagonistic lipopolysaccharide of Rhodobacter sphaeroides. Knocking down TLR4 using CRISPR/Cas9 also reduced regeneration quality, but not quantity, at the level of the cohort. However, we found that the editing level of individual tadpoles was a poor predictor of regenerative outcome. In conclusion, our results suggest that variable regeneration in refractory stage tadpoles depends at least in part on the skin microbiome and lipopolysaccharide signalling, but that signalling via TLR4 cannot account for all of this effect.

scholarly journals Probiotics to Prevent the Need for, and Augment the Use of, Antibiotics

2006 ◽  
Vol 17 (5) ◽  
pp. 291-295 ◽  
Author(s):  
Gregor Reid
Keyword(s):  
Health Benefit ◽  
Basic Research ◽  
Future Research ◽  
Regulatory Standards ◽  
Life Itself ◽  
Probiotic Strains ◽  
The Difference ◽  
Metabolic Properties ◽  
Probiotic Microbes

Although humans and microbes are inseparable, our knowledge and understanding of the majority of microbes that help keep us alive and well is in desperate need of further investigation. Of the organisms that influence humans before birth and inhabit various niches from birth to old age, we know little about their identity, origin, metabolic properties, attributes and mechanisms of interactions with the host and surrounding microbes. The use of probiotics ("live microorganisms which when administered in adequate amounts confer a health benefit on the host") has re-emerged as a means to restore and boost the beneficial microbes in our bodies. The timing of resurgent interest in this ancient field coincides with the need to augment or replace antibiotics whose side effects are unwelcome and whose efficacy is diminishing due to drug resistance. Evidence that probiotic strains can act as adjuncts to antibiotic therapy by reducing adverse effects, improving antibiotic function and enhancing mucosal immunity is mounting. It is to our discredit that basic research on microbial ecology has been stalled in Canada for the past 20 years. If supported, research into indigenous and probiotic microbes will form an important part of future research that sheds light on health, disease and a basic understanding of life itself. In some cases, probiotics will be the difference between a good quality of life and a bad one, or perhaps even life over death. Improvements in clinical studies, manufacturing and regulatory standards must coincide with this progress to ensure that physicians and consumers have reliable, proven products for safe and efficacious use.

T1257 Dual Effect of a Novel Toll-Like Receptor 4 (TLR4) Antagonist in Acute Murine Colitis

2008 ◽  
Vol 134 (4) ◽  
pp. A-517
Author(s):  
Ryan Ungaro ◽  
Masayuki Fukata ◽  
David Hsu ◽  
Yasmin Hernandez ◽  
Keith J. Breglio ◽  
...  
Keyword(s):  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Dual Effect ◽  
Murine Colitis ◽  
Tlr4 Antagonist

scholarly journals Comparative Toll-Like Receptor 4-Mediated Innate Host Defense to Bordetella Infection

2005 ◽  
Vol 73 (12) ◽  
pp. 8144-8152 ◽  
Author(s):  
Paul B. Mann ◽  
Daniel Wolfe ◽  
Eicke Latz ◽  
Douglas Golenbock ◽  
Andrew Preston ◽  
...  
Keyword(s):  
Host Defense ◽  
Hek293 Cells ◽  
Mouse Lung ◽  
Infection Model ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Closely Related Species ◽  
Mouse Infection Model ◽  
The Difference

ABSTRACT Bordetella pertussis, B. parapertussis, and B. bronchiseptica are closely related species associated with respiratory disease in humans and other mammals. While B. bronchiseptica has a wide host range, B. pertussis and B. parapertussis evolved separately from a B. bronchiseptica-like progenitor to naturally infect only humans. Despite very different doubling times in vitro, all three establish similar levels of infection in the mouse lung within 72 h. Recent work has revealed separate roles for Toll-like receptor 4 (TLR4) in immunity to B. pertussis and B. bronchiseptica, while no role for TLR4 during B. parapertussis infection has been described. Here we compared the requirement for TLR4 in innate host defense to these organisms using the same mouse infection model. While B. bronchiseptica causes lethal disease in TLR4-deficient mice, B. pertussis and B. parapertussis do not. Correspondingly, TLR4 is critical in limiting B. bronchiseptica but not B. pertussis or B. parapertussis bacterial numbers during the first 72 h. Interestingly, B. bronchiseptica induces a TLR4-dependent cytokine response that is considerably larger than that induced by B. pertussis or B. parapertussis. Analysis of their endotoxins using RAW cells suggests that B. bronchiseptica lipopolysaccharide (LPS) is 10- and 100-fold more stimulatory than B. pertussis or B. parapertussis LPS, respectively. The difference in LPS stimulus is more pronounced when using HEK293 cells expressing human TLR4. Thus, it appears that in adapting to infect humans, B. pertussis and B. parapertussis independently modified their LPS to reduce TLR4-mediated responses, which may compensate for slower growth rates and facilitate host colonization.

scholarly journals Antifibrotics and Antioxidants of Chlorogenic Acid Inhibits Toll- Like Receptors-4 as Liver Fibrotic Marker

2021 ◽  
Vol 3 (2) ◽  
pp. 91-99
Author(s):  
Rosdiana Naibey ◽  
Widya Wasityastuti ◽  
Nungki Anggorowati ◽  
Nur Arfian
Keyword(s):  
Chlorogenic Acid ◽  
Control Group ◽  
Toll Like Receptor ◽  
Rt Pcr ◽  
Toll Like Receptor 4 ◽  
Control Group Design ◽  
Body Tissues ◽  
Post Test ◽  
Group 3

Introduction: Chlorogenic Acid (CGA) is an antifibrotic and antioxidant for fibrotic tissues. These double  roles be able to inhibit or fibrotic tissues chains because of internal and external issues.  For example, virus, bacteria or other pathogens and also by drugs, alcohol, cigarettes, etc. as external factor that affect quality of body tissues. Toll-Like Receptor-4 (TLR-4) as a marker fibrotic tissues.  It is a key for researcher could be find out by expression performance. The aim of this study is to reveal the CGA as a candidate of antifibrotic & antioxidant in liver fibrosis that induced by CCL4.    Methods: This is a pure experimental research with a simple experimental design or post-test only control group design. The total 29 mices of 2.5-month-old male Swiss mices with weigh 35-40 gram divided into 6 group: 3 groups of controls (injected by natrium chloride, CGA, and CCL4) and 3 groups of treated (injected by CGA doses 42 mg/kg, 63 mg/kg or 84 mg/kg).  Liver organ was used to examine the expression of TLR-4 by rt-PCR. This research revealed that expression of TLR-4 lower than the CCL4 control group (respectively, p=0.042; p=0.005; p=0.006; and p=0.001). Higher dose of CGA showed greater ability as anti-fibrotic through inhibit the expression of  TLR-4. Some research found the expression of TLR-4 has been decreased by treatment of Clorogenic Acid (CGA). Conclusion: To sum up, CGA has double roles to repair liver fibrotic tissues. The greater doses of CGA, the stronger inhibition of TLR-4 expression.

scholarly journals Are Believers Happier than Atheists? Well-Being Measures in a Sample of Atheists and Believers in Puerto Rico

2018 ◽  
Author(s):  
Juan Aníbal González-Rivera ◽  
Adam Rosario-Rodríguez ◽  
Eduardo Rodríguez-Ramos ◽  
Idania Hernández-Gato ◽  
Lourdes Torres-Báez
Keyword(s):  
Quality Of Life ◽  
Life Satisfaction ◽  
Puerto Rico ◽  
Well Being ◽  
Social Awareness ◽  
Future Research ◽  
Average Difference ◽  
The Difference ◽  
Psychological Flourishing

Currently, not much has been written about the empirical psychological well-being of the atheist community in Puerto Rico and Latin America. The objective of the present study is to analyze if there are statistically significant differences in the levels of life satisfaction and psychological flourishing between believers in God and self-identified atheists. For this purpose, a sample of 821 participants (415 believers and 406 atheists) ranging from the ages of 19 to 85 years was selected. The results show that there is a slight average difference regarding life satisfaction and psychological flourishing between these groups; however, the difference is not substantial enough to ensure that believers in God or atheists have a better quality of life. Both believers and atheists exhibit high levels of life satisfaction and psychological flourishing. This study provides empirical evidence to demystify certain traditional assumptions about the supremacy of religious beliefs over secular convictions or vice versa. We hope that these findings create social awareness and could be used as a basis for future research concerning the population of non-believers.

scholarly journals Excavation of Genes Related to the Mining of Growth, Development, and Meat Quality of Two Crossbred Sheep Populations Based on Comparative Transcriptomes

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1492
Author(s):  
Jinping Shi ◽  
Xueying Wang ◽  
Yali Song ◽  
Ting Liu ◽  
Shuru Cheng ◽  
...  
Keyword(s):  
Meat Quality ◽  
Transcriptome Analysis ◽  
Muscle Development ◽  
Bioinformatic Analysis ◽  
Production Performance ◽  
Future Research ◽  
Productive Performance ◽  
Growth Development ◽  
Better Than

Crossbreeding can improve production performance and meat quality in sheep. The objective of this study was to look for genes related to sheep growth, development, and muscle. In this study, Dorper (DP) × Small Tailed Han (STH) sheep and Mongolia (MG) × Small-tailed Han (STH) sheep were used to estimate the productive performance and meat quality in a crossbreed. Subsequently, transcriptome analysis and bioinformatic analysis were performed on the Longissimus dorsi muscles of DP × STH and MG × STH sheep to identify differentially expressed genes (DEGs) related to growth, development, and meat quality. The presence of DEGs was confirmed by real-time PCR (qPCR). Productive performance and meat quality of the DP × STH sheep were better than the MG × STH sheep. Compared to DP × STH, a total of 1445 DEGs were identified in MG × STH sheep (1026 DEG were up-regulated and 419 DEG were down-regulated). Of these, 38 DEGs were related to growth, 161 to development, and 43 to muscle. In addition, 13 co-expressed genes (FGFRL1, SIX1, PLCB1, CRYAB, MYL2, ADIPOQ, GPX1, PPARD, GPC1, CDC42, LOC101106246, IGF1, and LARGE) were identified. The expression of DEGs was consistent with the comparative transcriptome analysis. This work provides genetics resources for future research on muscle development in sheep.

Comparative Effects of High-Tech Visual Scene Displays and Low-Tech Isolated Picture Symbols on Engagement From Students With Multiple Disabilities

2019 ◽  
Vol 50 (4) ◽  
pp. 693-702 ◽  
Author(s):  
Christine Holyfield ◽  
Sydney Brooks ◽  
Allison Schluterman
Keyword(s):  
Language Learning ◽  
Augmentative And Alternative Communication ◽  
Visual Analysis ◽  
Multiple Disabilities ◽  
Visual Scene ◽  
Future Research ◽  
High Tech ◽  
Single Subject ◽  
Wide Range ◽  
The Difference

Purpose Augmentative and alternative communication (AAC) is an intervention approach that can promote communication and language in children with multiple disabilities who are beginning communicators. While a wide range of AAC technologies are available, little is known about the comparative effects of specific technology options. Given that engagement can be low for beginning communicators with multiple disabilities, the current study provides initial information about the comparative effects of 2 AAC technology options—high-tech visual scene displays (VSDs) and low-tech isolated picture symbols—on engagement. Method Three elementary-age beginning communicators with multiple disabilities participated. The study used a single-subject, alternating treatment design with each technology serving as a condition. Participants interacted with their school speech-language pathologists using each of the 2 technologies across 5 sessions in a block randomized order. Results According to visual analysis and nonoverlap of all pairs calculations, all 3 participants demonstrated more engagement with the high-tech VSDs than the low-tech isolated picture symbols as measured by their seconds of gaze toward each technology option. Despite the difference in engagement observed, there was no clear difference across the 2 conditions in engagement toward the communication partner or use of the AAC. Conclusions Clinicians can consider measuring engagement when evaluating AAC technology options for children with multiple disabilities and should consider evaluating high-tech VSDs as 1 technology option for them. Future research must explore the extent to which differences in engagement to particular AAC technologies result in differences in communication and language learning over time as might be expected.

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