scholarly journals Gels for constant and smart delivery of insulin

2020 ◽  
Vol 20 (1) ◽  
pp. 41-51
Author(s):  
M Joan Taylor ◽  
Krishan P Chauhan ◽  
Tarsem S Sahota
Keyword(s):  
Closed Loop ◽  
Peripheral Tissue ◽  
Hepatic Glycogen ◽  
Rheological Characteristics ◽  
Ligand Interaction ◽  
Orally Active ◽  
Cohesive Materials ◽  
Programmed Release

The focus of this review is the role of gelatinous materials for oral, transdermal and peritoneal insulin platforms as alternatives to the ubiquitous subcutaneous depot approach. Hydrogels that form hydrated, cohesive materials and the topologically complex micellar types can add ligand interaction, bond vulnerability and rheological characteristics to develop reliable programmed release, including closed loop (automated basal and bolus) activity in non-oral routes. In addition, the potential protection of the protein and likely increased paracellular uptake mean that orally active insulin is feasible. While unlikely to be suitable for closed loop delivery, the driver for gut absorption is not only to increase the convenience and decrease dosage trauma, but to target the mesentery-portal vasculature rather than peripheral tissue, thus improving hepatic glycogen equilibrium and reducing the obesogenic effect and hypoglycaemic episodes.

scholarly journals Peripheral tissue–brain interactions in the regulation of food intake

2007 ◽  
Vol 66 (1) ◽  
pp. 131-155 ◽  
Author(s):  
Miguel López ◽  
Sulay Tovar ◽  
María J. Vázquez ◽  
Lynda M. Williams ◽  
Carlos Diéguez
Keyword(s):  
Fatty Acid Synthase ◽  
Molecular Mechanisms ◽  
Developed Countries ◽  
Peripheral Tissue ◽  
Feeding Regulation ◽  
Pharmacological Targets ◽  
The Central Nervous System ◽  
Treatment Of Obesity ◽  
Brain Interactions

More than 70 years ago the glucostatic, lipostatic and aminostatic hypotheses proposed that the central nervous system sensed circulating levels of different metabolites, changing feeding behaviour in response to the levels of those molecules. In the last 20 years the rapid increase in obesity and associated pathologies in developed countries has involved a substantial increase in the knowledge of the physiological and molecular mechanism regulating body mass. This effort has resulted in the recent discovery of new peripheral signals, such as leptin and ghrelin, as well as new neuropeptides, such as orexins, involved in body-weight homeostasis. The present review summarises research into energy balance, starting from the original classical hypotheses proposing metabolite sensing, through peripheral tissue–brain interactions and coming full circle to the recently-discovered role of hypothalamic fatty acid synthase in feeding regulation. Understanding these molecular mechanisms will provide new pharmacological targets for the treatment of obesity and appetite disorders.

scholarly journals Advances in the Identification of Circular RNAs and Research Into circRNAs in Human Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Shihu Jiao ◽  
Song Wu ◽  
Shan Huang ◽  
Mingyang Liu ◽  
Bo Gao
Keyword(s):  
Neurological Disorders ◽  
Closed Loop ◽  
Significant Proportion ◽  
Human Diseases ◽  
Circular Rnas ◽  
The Status ◽  
Research Questions ◽  
Non Coding Rnas ◽  
Microrna Sponges

Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs (ncRNAs) with a closed-loop structure that are mainly produced by variable processing of precursor mRNAs (pre-mRNAs). They are widely present in all eukaryotes and are very stable. Currently, circRNA studies have become a hotspot in RNA research. It has been reported that circRNAs constitute a significant proportion of transcript expression, and some are significantly more abundantly expressed than other transcripts. CircRNAs have regulatory roles in gene expression and critical biological functions in the development of organisms, such as acting as microRNA sponges or as endogenous RNAs and biomarkers. As such, they may have useful functions in the diagnosis and treatment of diseases. CircRNAs have been found to play an important role in the development of several diseases, including atherosclerosis, neurological disorders, diabetes, and cancer. In this paper, we review the status of circRNA research, describe circRNA-related databases and the identification of circRNAs, discuss the role of circRNAs in human diseases such as colon cancer, atherosclerosis, and gastric cancer, and identify remaining research questions related to circRNAs.

Glycomic and glycotranscriptomic profiling of mucin-type O-glycans in planarian Schmidtea mediterranea

Glycobiology ◽  
2021 ◽  
Author(s):  
Sabarinath Peruvemba Subramanian ◽  
Vairavan Lakshmanan ◽  
Dasaradhi Palakodeti ◽  
Ramaswamy Subramanian
Keyword(s):  
Tissue Regeneration ◽  
Cell Biology ◽  
Schmidtea Mediterranea ◽  
Ligand Interaction ◽  
Differentiated Cells ◽  
Cell Matrix ◽  
Composition And Structure ◽  
Enzyme Class ◽  
Cell Cell

Abstract O-Glycans on cell surfaces play important roles in cell-cell, cell-matrix, and receptor-ligand interaction. Therefore, glycan-based interactions are important for tissue regeneration and homeostasis. Free-living flatworm Schmidtea mediterranea, because of its robust regenerative potential, is of great interest in the field of stem cell biology and tissue regeneration. Nevertheless, information on the composition and structure of O-glycans in planaria is unknown. Using mass spectrometry and in silico approaches, we characterized the glycome and the related transcriptome of mucin-type O-glycans of planarian S. mediterranea. Mucin-type O-glycans were composed of multiple isomeric, methylated, and unusually extended mono- and di-substituted O-GalNAc structures. Extensions made of hexoses and 3-O methyl hexoses were the glycoforms observed. From glycotranscriptomic analysis, sixty genes belonging to five distinct enzyme classes were identified to be involved in mucin-type O-glycan biosynthesis. These genes shared homology with those in other invertebrate systems. While a majority of the genes involved in mucin-type O-glycan biosynthesis was highly expressed during organogenesis and in differentiated cells, a few select genes in each enzyme class were specifically enriched during early embryogenesis. Our results indicate a unique temporal and spatial role for mucin-type O-glycans during embryogenesis and organogenesis and in adulthood. In summary, this is the first report on O-glycans in planaria. This study expands the structural and biosynthetic possibilities in cellular glycosylation in the invertebrate glycome and provides a framework towards understanding the biological role of mucin-type O-glycans in tissue regeneration using planarians.

Pathway and carbon sources for hepatic glycogen repletion in dogs

1991 ◽  
Vol 260 (2) ◽  
pp. E194-E202 ◽  
Author(s):  
A. Mitrakou ◽  
R. Jones ◽  
Y. Okuda ◽  
J. Pena ◽  
N. Nurjhan ◽  
...  
Keyword(s):  
Carbon Sources ◽  
Hepatic Uptake ◽  
Hepatic Glycogen ◽  
Oral Glucose ◽  
Indirect Pathway ◽  
Hepatic Glucose ◽  
Glycogen Repletion ◽  
Hepatic Glucose Uptake ◽  
Labeling Pattern

The present studies were undertaken to quantitate the relative contributions of the indirect and direct pathways for hepatic glycogen repletion and to determine the role of splanchnic tissues in provision of C precursors used for the indirect pathway. For this purpose, we administered oral glucose (1.4 g/kg) enriched with [1-14C]glucose to 18-h fasted dogs and measured net hepatic and net gastrointestinal glucose, lactate, and alanine balance, hepatic and gastrointestinal fractional extraction [( 3H]lactate), release and uptake of lactate, as well as the total amount of hepatic glycogen formed from the oral glucose and the 14C labeling pattern of the glycogen-glucose C. Although net hepatic glucose uptake (8.7 +/- 0.6 g, 27% of the oral load) exceeded the amount of glycogen formed from the oral glucose (6.3 +/- 1.1 g), analysis of radioactivity in C-1 of the glycogen glucose indicated that nearly 50% of the glycogen was formed by the indirect pathway. Net hepatic uptake of lactate (1.4 +/- 0.1 g) and alanine (1.5 +/- 0.1 g) could account for greater than 90% of glycogen formed by the indirect pathway if all of the lactate and alanine taken up by the liver had been incorporated into glycogen. Release of lactate and alanine by splanchnic tissues approximated the amount of lactate and alanine taken up by the liver. However, in addition to taking up lactate, the liver also produced nearly as much lactate as the gastrointestinal tract (1.8 +/- 0.2 vs. 2.0 +/- 0.3 g, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals An Anti-MICA/B Antibody and IL-15 Rescue Altered NKG2D-Dependent NK Cell Responses in Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3583
Author(s):  
Stefania Mantovani ◽  
Stefania Varchetta ◽  
Dalila Mele ◽  
Matteo Donadon ◽  
Guido Torzilli ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Protein A ◽  
Ligand Interaction ◽  
Cell Responses ◽  
Hcc Cells

Natural killer (NK) cells play a pivotal role in cancer immune surveillance, and activating the receptor/ligand interaction may contribute to control the development and evolution of hepatocellular carcinoma (HCC). We investigated the role of the natural killer group 2 member D (NKG2D) activating receptor and its ligand, the major histocompatibility complex class I chain-related protein A and B (MICA/B) in patients with cirrhosis and HCC subjected to surgical resection, patients with cirrhosis and no HCC, and healthy donors (HD). The NKG2D-mediated function was determined in peripheral blood (PB), in tumor-infiltrating lymphocytes (NK-TIL), and in matched surrounding liver tissue (NK-LIL). A group of patients treated with sorafenib because of clinically advanced HCC was also studied. A humanized anti-MICA/B monoclonal antibody (mAb) was used in in vitro experiments to examine NK cell-mediated antibody-dependent cellular cytotoxicity. Serum concentrations of soluble MICA/B were evaluated by ELISA. IL-15 stimulation increased NKG2D-dependent activity which, however, remained dysfunctional in PB NK cells from HCC patients, in line with the reduced NKG2D expression on NK cells. NK-TIL showed a lower degranulation ability than NK-LIL, which was restored by IL-15 stimulation. Moreover, in vitro IL-15 stimulation enhanced degranulation and interferon-γ production by PB NK from patients at month one of treatment with sorafenib. Anti-MICA/B mAb associated with IL-15 was able to induce PB NK cytotoxicity for primary HCC cells in HD and patients with HCC, who also showed NK-TIL degranulation for autologous primary HCC cells. Our findings highlight the key role of the NKG2D-MICA/B axis in the regulation of NK cell responses in HCC and provide evidence in support of a potentially important role of anti-MICA/B mAb and IL-15 stimulation in HCC immunotherapy.

The Role of Closed-Loop Hand Control in Handshaking Interactions

2019 ◽  
Vol 4 (2) ◽  
pp. 878-885 ◽  
Author(s):  
Francesco Vigni ◽  
Espen Knoop ◽  
Domenico Prattichizzo ◽  
Monica Malvezzi
Keyword(s):  
Closed Loop ◽  
Hand Control

The Critical Role of Fas-Fas Ligand Interaction in Donor-Specific Transfusion-Induced Tolerance to H-Y Antigen

2004 ◽  
Vol 78 (6) ◽  
pp. 799-806 ◽  
Author(s):  
Ryosuke Minagawa ◽  
Shinji Okano ◽  
Yukihiro Tomita ◽  
Kenji Kishihara ◽  
Hisakata Yamada ◽  
...  
Keyword(s):  
Fas Ligand ◽  
Critical Role ◽  
Ligand Interaction ◽  
Induced Tolerance

Role of the 14-3-3 C-terminal loop in ligand interaction

2002 ◽  
Vol 49 (3) ◽  
pp. 321-325 ◽  
Author(s):  
Amy B. Truong ◽  
Shane C. Masters ◽  
Hongzhu Yang ◽  
Haian Fu
Keyword(s):  
Ligand Interaction ◽  
Terminal Loop

scholarly journals Update on Peripheral Arterial Vasodilation, Ascites and Hepatorenal Syndrome in Cirrhosis

2000 ◽  
Vol 14 (suppl d) ◽  
pp. 112D-121D ◽  
Author(s):  
Mladen Knotek ◽  
Boris Rogachev ◽  
Robert W Schrier
Keyword(s):  
Hepatorenal Syndrome ◽  
Decompensated Cirrhosis ◽  
Arterial Tree ◽  
Salt Diet ◽  
Bacterial Peritonitis ◽  
Low Salt ◽  
Intrahepatic Portosystemic Shunt ◽  
Peripheral Arterial ◽  
Orally Active

In cirrhosis of the liver, according to the peripheral arterial vasodilation hypothesis, relative underfilling of the arterial tree triggers a neurohumoral response (activation of renin-angiotensinaldosterone system, sympathetic nervous system, nonosmotic release of vasopressin) aimed at restoring circulatory integrity by promoting renal sodium and water retention. Evidence has accumulated for a major role of increased vascular production of nitric oxide as the primary cause of arterial vasodilation in cirrhosis. Ascites is a common complication in cirrhosis. Treatment of ascites consists of a low salt diet with diuretics, and paracentesis together with plasma volume expanders in diuretic-resistant patients. Progression of cirrhosis may result in hepatorenal syndrome, a state of functional renal failure that carries an ominous prognosis. Orthotopic liver transplantation has remained the only curative treatment for patients with advanced liver disease; other modalities such as transjugular intrahepatic portosystemic shunt or vasopressin analogues may serve as a bridge to transplantation. Another complication of decompensated cirrhosis is spontaneous bacterial peritonitis, the incidence of which can be reduced by primary or secondary antibiotic prophylaxis by using orally active antibiotics.

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