scholarly journals Polyelectrolytes Formulated with Primary Unconjugated Bile Acid Optimised Pharmacology of Bio-Engineered Implant

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1713
Author(s):  
Armin Mooranian ◽  
Corina Mihaela Ionescu ◽  
Susbin Raj Wagle ◽  
Bozica Kovacevic ◽  
Daniel Walker ◽  
...  
Keyword(s):  
Bile Acid ◽  
Lithocholic Acid ◽  
Biological Effects ◽  
Interleukin 1 ◽  
Interleukin 12 ◽  
Post Transplantation ◽  
Beneficial Effects ◽  
Inflammatory Profile ◽  
Factor Α

Introduction. Several studies have shown that different biomaterials and hydrogels comprising various bile acids such as chenodeoxycholic acid (CDCA), as well as excipients such as poly-(styrene)-sulphonate (PSS) and poly-(allyl)-amine (PAA), exhibited positive biological effects on encapsulated viable pancreatic β-cells. Hence, this study aimed to investigate whether incorporating CDCA with PSS and PAA will optimise the functions of encapsulated pancreatic islets post-transplantation in Type 1 diabetes (T1D). Methods. Mice were made T1D, divided into two equal groups, and transplanted with encapsulated islets in PSS-PAA (control) or with CDCA-PSS-PAA (treatment) microcapsules. The effects of transplanted microcapsules on blood glucose, inflammation and the bile acid profile were measured post-transplantation. Results and Conclusion. Compared with control, the treatment group showed better survival rate, improved glycaemic control, and lower inflammatory profile, illustrated by ↓ interleukin 1-β, interleukin-6, interleukin-12, and tumour-necrosis factor-α, and ↓ levels of the bile acid, as well as lithocholic acid in the plasma, liver, large intestine and faeces. The results suggest that CDCA incorporation with PSS-PAA microcapsules exerted beneficial effects on encapsulated islets and resulted in enhanced diabetes treatment, post-transplantation, at the local and systemic levels.

scholarly journals Taurine Grafted Micro-Implants Improved Functions without Direct Dependency between Interleukin-6 and the Bile Acid Lithocholic Acid in Plasma

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 111
Author(s):  
Armin Mooranian ◽  
Corina Mihaela Ionescu ◽  
Susbin Raj Wagle ◽  
Bozica Kovacevic ◽  
Daniel Walker ◽  
...  
Keyword(s):  
Bile Acid ◽  
Interleukin 6 ◽  
Lithocholic Acid ◽  
Biological Effects ◽  
Post Transplantation ◽  
Mature Adult ◽  
Beneficial Effects ◽  
Adult Mice ◽  
Diabetes Development ◽  
Micro Implants

A recent study showed an association between diabetes development and the bile acid lithocholic acid (LCA), while another study demonstrated positive biological effects of the conjugated bile acid, taurocholic acid (TCA), on pancreatic cells. Thus, this study aimed to encapsulate TCA with primary islets (graft) and study the biological effects of the graft, post-transplantation, in diabetic mice, including effects on LCA concentrations. Sixteen mature adult mice were made diabetic and randomly divided into two equal groups, control and test (transplanted encapsulated islets without or with TCA). Graft pharmaceutical features pre-transplantation, and biological effects including on LCA concentrations post-transplantation, were measured. TCA-microcapsules had an oval shape and similar size compared with the control. The treatment group survived longer, showed improved glucose and interleukin-6 concentrations, and lower LCA concentrations in plasma, large intestine, faeces, liver and spleen, compared with control. Results suggest that TCA incorporation with islets encapsulated graft exerted beneficial effects, but there was no direct and significant dependency between concentrations of interleukin-6 and LCA.

Histological effects of pharmacologically active human bile acid nano/micro-particles in Type-1 diabetes

2020 ◽  
Vol 11 (3) ◽  
pp. 157-171
Author(s):  
Sangeetha Mathavan ◽  
Corina M Ionescu ◽  
Bozica Kovacevic ◽  
Momir Mikov ◽  
Svetlana Golocorbin-Kon ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Bile Acid ◽  
Drug Formulation ◽  
Human Bile ◽  
Beneficial Effects ◽  
Micro Particles ◽  
Anti Inflammatory ◽  
Pharmacologically Active

Aim: Gliclazide (G) is a drug prescribed for Type 2 diabetics, although recent studies suggest it has desirable effects in both types of diabetes, Type 1 diabetes and Type 2 diabetes. G has an inconsistent absorption due to poor formulation and bile acids (BAs) have shown significant promise in drug formulation optimization. Hence, the study aimed to examine G effects on histopathological, anti-inflammatory and antidiabetic effects when encapsulated with BAs. Materials & methods: Rats were randomized into eight groups, of which seven were made Type 1 diabetes and treated with various BA-based treatments. Tissue histopathology, inflammation and the bile acid profile were analyzed. Results & conclusion: G capsules showed no histological but the most anti-inflammatory effects, which suggest significant beneficial effects in diabetes treatment.

Modulatory Nano/Micro Effects of Diabetes Development on Pharmacology of Primary and Secondary Bile Acids Concentrations

2020 ◽  
Vol 16 (8) ◽  
pp. 900-909
Author(s):  
Armin Mooranian ◽  
Nassim Zamani ◽  
Ryu Takechi ◽  
Giuseppe Luna ◽  
Momir Mikov ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Lithocholic Acid ◽  
Secondary Bile Acid ◽  
Feedback Mechanisms ◽  
Diabetes Development ◽  
Bile Acid Profiles ◽  
Secondary Bile Acids

Background: Recent studies have suggested that hyperglycaemia influences the bile acid profile and concentrations of secondary bile acids in the gut. Introduction: This study aimed to measure changes in the bile acid profile in the gut, tissues, and faeces in type 1 Diabetes (T1D) and Type 2 Diabetes (T2D). Method: T1D and T2D were established in a mouse model. Twenty-one seven-weeks old balb/c mice were randomly divided into three equal groups, healthy, T1D and T2D. Blood, tissue, urine and faeces samples were collected for bile acid measurements. Results: Compared with healthy mice, T1D and T2D mice showed lower levels of the primary bile acid, chenodeoxycholic acid, in the plasma, intestine, and brain, and higher levels of the secondary bile acid, lithocholic acid, in the plasma and pancreas. Levels of the bile acid ursodeoxycholic acid were undetected in healthy mice but were found to be elevated in T1D and T2D mice. Conclusion: Bile acid profiles in other organs were variably influenced by T1D and T2D development, which suggests similarity in effects of T1D and T2D on the bile acid profile, but these effects were not always consistent among all organs, possibly since feedback mechanisms controlling enterohepatic recirculation and bile acid profiles and biotransformation are different in T1D and T2D.

Role of adapters in Toll-like receptor signalling

2003 ◽  
Vol 31 (3) ◽  
pp. 637-642 ◽  
Author(s):  
S. Akira ◽  
M. Yamamoto ◽  
K. Takeda
Keyword(s):  
Biological Effects ◽  
Interleukin 1 ◽  
Critical Role ◽  
Nuclear Factor Κb ◽  
The Body ◽  
Receptor Signalling ◽  
Signalling Molecule ◽  
Repeat Domain

Toll-like receptors (TLRs) play a critical role in the detection of invading pathogens within the body and the subsequent immune response. Individual TLRs recognize distinct microbial components. The TLRs are a type 1 transmembrane receptor that possess an extracellular leucine-rich repeat domain and cytoplasmic domain homologous with that of the interleukin 1 receptor (IL-1R) family. Upon stimulation, TLR recruits the IL-1R-associated kinase (IRAK) via the adapter MyD88, ultimately leading to the activation of nuclear factor-κB. Cytokine production in response to all TLR ligands is completely abolished in MyD88-deficient cells, indicating that MyD88 is an essential signalling molecule shared among members of the IL-1R/Toll family. However, several novel adaptor molecules have recently been identified. Evidence is now accumulating showing that differential utilization of these adaptors may activate overlapping as well as distinct signalling pathways, and ultimately give rise to distinct biological effects exerted by individual TLR family members.

Role of interleukin-1 in the pulmonary immune response duringPseudomonas aeruginosapneumonia

2002 ◽  
Vol 282 (2) ◽  
pp. L285-L290 ◽  
Author(s):  
Marc J. Schultz ◽  
Anita W. Rijneveld ◽  
Sandrine Florquin ◽  
Carl K. Edwards ◽  
Charles A. Dinarello ◽  
...  
Keyword(s):  
Pulmonary Infection ◽  
Interleukin 1 ◽  
Wild Type ◽  
Inflammatory Protein ◽  
Colony Forming Units ◽  
Factor Α ◽  
Macrophage Inflammatory Protein ◽  
Necrosis Factor

Pneumonia is associated with elevated concentrations of the proinflammatory cytokine interleukin (IL)-1 in the pulmonary compartment. To study the role of IL-1 in the pathogenesis of Pseudomonas pneumonia, IL-1 receptor type 1 gene-deficient ( IL-1R −/−) mice and wild-type mice were intranasally inoculated with Pseudomonas aeruginosa. The absence of the IL-1 signal attenuated the outgrowth of Pseudomonas in lungs, as reflected by an increasing number of colony-forming units (cfu) during Pseudomonaspneumonia in wild-type mice and a concurrently decreasing number of cfu during pulmonary infection in IL-1R −/− mice ( P < 0.05, IL-1R −/− mice vs. wild-type mice). Influx of neutrophils was decreased in bronchoalveolar lavage fluids in IL-1R −/− mice compared with wild-type mice. Similarly, lung levels of cytokines (tumor necrosis factor-α, IL-6) and chemokines (macrophage inflammatory protein-2 and KC) were lower in IL-1R −/− mice 24 h postinoculation. Consistent with results obtained in IL-1R −/− mice, treatment of wild-type mice with IL-1R antagonist also diminished outgrowth of Pseudomonas when compared with wild-type mice treated with vehicle ( P < 0.05). These results demonstrate that an absence or reduction in endogenous IL-1 activity improves host defense against Pseudomonas pneumonia while suppressing the inflammatory response.

scholarly journals Anti-aging and anti-carcinogenic effects of 1α, 25-dihyroxyvitamin D3 on skin

2022 ◽  
Author(s):  
Neena Philips ◽  
Mikel Portillo-Esnaola ◽  
Philips Samuel ◽  
Maria Gallego-Rentero ◽  
Tom Keller ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Transforming Growth Factor Β ◽  
Vitamin D Supplementation ◽  
Ecm Remodeling ◽  
Beneficial Effects ◽  
Factor Α ◽  
Oxidative Effects ◽  
Endothelial Growth Factor

Photoaging and carcinogenesis are facilitated by oxidative stress, inflammation, angiogenesis, and extracellular matrix (ECM) remodeling. Oxidative effects include DNA damage, membrane oxidation, lipid peroxidation, and alterations in the expression of p53 and antioxidant enzymes. The inflammatory and angiogenesis mediators include interleukin-1, tumor necrosis factor-α, interleukin-8, transforming growth factor-β, and vascular endothelial growth factor. ECM remodeling includes alterations in the expression and organization of collagen, elastin, matrix metalloproteinases, and elastase. 1α, 25-dihydroxy-vitamin D3 has antioxidant, anti-inflammatory, and ECM regulatory properties, and can counteract the processes that facilitate photoaging and carcinogenesis. This review provides an overview of the beneficial effects of vitamin D supplementation at a molecular level, followed by a brief discussion regarding its use as a supplement.

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