•Obestatin is 23-mer C-terminally amidated peptide is derived from preproghrelin.•It has been ascribed a wide range of metabolic effects relevant to type 2 diabetes.•Its biochemical properties ...(structure, sequence, stability and distribution) are reviewed.•A balanced examination of the many reported pancreatic and extrapancreatic actions.
Obestatin was initially discovered in rat stomach extract, and although it is principally produced in the gastric mucosa, it can be found throughout the gastrointestinal tract. This 23-amino acid C-terminally amidated peptide is derived from preproghrelin and has been ascribed a wide range of metabolic effects relevant to type 2 diabetes. Obestatin reportedly inhibits gastrointestinal motility, reduces food intake and lowers body weight and improves lipid metabolism. Furthermore, it appears to exert actions on the pancreatic β-cell, most notably increasing β-cell mass and upregulating genes associated with insulin production and β-cell regeneration, with relevance to type 2 diabetes. It is becoming evident that obestatin also exerts pleiotropic effects on the cardiovascular system, possibly modulating blood pressure, endothelial function and triggering cardioprotective mechanisms, which may be important in determining cardiovascular outcomes in type 2 diabetes. Furthermore, it seems that like other gut peptides obestatin has neuroprotective properties. This review examines the biochemical properties of the obestatin peptide (its structure, sequence, stability and distribution) and the candidate receptors through which it may act. It provides a balanced examination of the reported pancreatic and extrapancreatic actions of obestatin and evaluates its potential relevance with respect to diabetes therapy, together with discussion of direct evidence linking alterations in obestatin signalling with obesity/diabetes and other diseases.
To advance a novel concept of debulking virus in the oral cavity, the primary site of viral replication, virus-trapping proteins CTB-ACE2 were expressed in chloroplasts and clinical-grade plant ...material was developed to meet FDA requirements. Chewing gum (2 g) containing plant cells expressed CTB-ACE2 up to 17.2 mg ACE2/g dry weight (11.7% leaf protein), have physical characteristics and taste/flavor like conventional gums, and no protein was lost during gum compression. CTB-ACE2 gum efficiently (>95%) inhibited entry of lentivirus spike or VSV-spike pseudovirus into Vero/CHO cells when quantified by luciferase or red fluorescence. Incubation of CTB-ACE2 microparticles reduced SARS-CoV-2 virus count in COVID-19 swab/saliva samples by >95% when evaluated by microbubbles (femtomolar concentration) or qPCR, demonstrating both virus trapping and blocking of cellular entry. COVID-19 saliva samples showed low or undetectable ACE2 activity when compared with healthy individuals (2,582 versus 50,126 ΔRFU; 27 versus 225 enzyme units), confirming greater susceptibility of infected patients for viral entry. CTB-ACE2 activity was completely inhibited by pre-incubation with SARS-CoV-2 receptor-binding domain, offering an explanation for reduced saliva ACE2 activity among COVID-19 patients. Chewing gum with virus-trapping proteins offers a general affordable strategy to protect patients from most oral virus re-infections through debulking or minimizing transmission to others.
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With a large majority of the global population unvaccinated and outbreaks of variants with higher viral load, new methods are needed to decrease SARS-CoV-2 transmission and infection. Daniell et al. report that chewing gum containing plant cells expressing angiotensin-converting enzyme 2 efficiently traps SARS-CoV-2 in COVID-19 patient saliva or swab samples.
Green, BS, Blake C, and Caulfield, BM. A valid field test protocol of linear speed and agility in rugby union. J Strength Cond Res 25(5)1256-1262, 2011-Field testing is a key component to measure ...player performance in all sports, which provides coaches and strength and conditioning staff information to evaluate player performance and measure desired training effects. Therefore, the purpose of this study was to investigate the reliability and construct validity of a rugby union field test protocol based on analysis of the components of the game. Participants were placed in an Academy (n = 17) or Club (n = 11) group determined by current playing level. Trials of 10- and 30-m linear speed (LS), change of direction speed, and reactive agility speed were measured to evaluate the field test protocolʼs utility in distinguishing players of different playing abilities. Reliability analysis of each field test demonstrated stable values allowing this field test protocol to be used to compare between groups. Furthermore, the Academy players performed significantly (p < 0.05) faster compared to Club players in all LS and agility components. These results suggest that this field test protocol is appropriate to identify rugby union players of varying playing abilities allowing coaches and strength and fitness staff to measure a playerʼs capability to execute critical aspects of the game and may have application in performance evaluation and talent identification. The results from this study suggest that this test battery is an appropriate measure in identifying the varying playing abilities of rugby union players. This enables coaches and fitness staff to assess a playerʼs capability in executing critical aspects of the game and also may have application in performance evaluation and talent identification.
Delirium is an acute change in attention and cognition occurring in ~ 65% of severe SARS-CoV-2 cases. It is also common following surgery and an indicator of brain vulnerability and risk for the ...development of dementia. In this work we analyzed the underlying role of metabolism in delirium-susceptibility in the postoperative setting using metabolomic profiling of cerebrospinal fluid and blood taken from the same patients prior to planned orthopaedic surgery. Distance correlation analysis and Random Forest (RF) feature selection were used to determine changes in metabolic networks. We found significant concentration differences in several amino acids, acylcarnitines and polyamines linking delirium-prone patients to known factors in Alzheimer's disease such as monoamine oxidase B (MAOB) protein. Subsequent computational structural comparison between MAOB and angiotensin converting enzyme 2 as well as protein-protein docking analysis showed that there potentially is strong binding of SARS-CoV-2 spike protein to MAOB. The possibility that SARS-CoV-2 influences MAOB activity leading to the observed neurological and platelet-based complications of SARS-CoV-2 infection requires further investigation.
Certain endogenous bile acids have been proposed as potential therapies for ameliorating Alzheimer's disease (AD) but their role, if any, in the pathophysiology of this disease is not currently ...known. Given recent evidence of bile acids having protective and anti-inflammatory effects on the brain, it is important to establish how AD affects levels of endogenous bile acids. Using LC-MS/MS, this study profiled 22 bile acids in brain extracts and blood plasma from AD patients (n = 10) and age-matched control subjects (n = 10). In addition, we also profiled brain/plasma samples from APP/PS1 and WT mice (aged 6 and 12 months). In human plasma, we detected significantly lower cholic acid (CA, p = 0.03) in AD patients than age-matched control subjects. In APP/PS1 mouse plasma we detected higher CA (p = 0.05, 6 months) and lower hyodeoxycholic acid (p = 0.04, 12 months) than WT. In human brain with AD pathology (Braak stages V-VI) taurocholic acid (TCA) were significantly lower (p = 0.01) than age-matched control subjects. In APP/PS1 mice we detected higher brain lithocholic acid (p = 0.05) and lower tauromuricholic acid (TMCA; p = 0.05, 6 months). TMCA was also decreased (p = 0.002) in 12-month-old APP/PS1 mice along with 5 other acids: CA (p = 0.02), β-muricholic acid (p = 0.02), Ω-muricholic acid (p = 0.05), TCA (p = 0.04), and tauroursodeoxycholic acid (p = 0.02). The levels of bile acids are clearly disturbed during the development of AD pathology and, since some bile acids are being proposed as potential AD therapeutics, we demonstrate a method that can be used to support work to advance bile acid therapeutics.
The COVID-19 pandemic created a globally shared stressor that saw a rise in the emphasis on mental and emotional wellbeing. However, historically, these topics were not openly discussed, leaving ...those struggling without professional support. One powerful tool to bridge the gap and facilitate connectedness during times of isolation is online health communities (OHCs). This study surveyed Health Union OHC members during the pandemic to determine the degree of COVID-19 concern, social isolation, and mental health distress they are facing, as well as to assess where they are receiving information about COVID-19 and what sources of support they desire. The survey was completed in six independent waves between March 2020 and April 2021, and garnered 10,177 total responses. In the United States, OHCs were utilized significantly more during peak lockdown times, and the desire for emotional and/or mental health support increased over time. Open-ended responses demonstrated a strong desire for connection and validation, which are quintessential characteristics of OHCs. Through active moderation utilizing trained moderators, OHCs can provide a powerful, intermediate and safe space where conversations about mental and emotional wellbeing can be normalized and those in need are encouraged to seek additional assistance from healthcare professionals if warranted.
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Cell replacement therapies are often enhanced by utilizing polymer scaffolds to improve retention or direct cell orientation and migration. Obstacles to refinement of such polymer ...scaffolds often include challenges in controlling the microstructure of biocompatible molecules in three dimensions at cellular scales. Two-photon polymerization of acrylated poly(caprolactone) (PCL) could offer a means of achieving precise microstructural control of a material in a biocompatible platform. In this work, we studied the effect of various formulation and two-photon polymerization parameters on minimum laser power needed to achieve polymerization, resolution, and fidelity to a target 3D model designed to be used for retinal cell replacement. Overall, we found that increasing the concentration of crosslink-able groups decreased polymerization threshold and the size of resolvable features while increasing fidelity of the scaffold to the 3D model. In general, this improvement was achieved by increasing the number of acrylate groups per prepolymer molecule, increasing the acrylated PCL concentration, or decreasing its molecular weight. Resulting two-photon polymerized PCL scaffolds successfully supported human iPSC derived retinal progenitor cells in vitro. Sub-retinal implantation of cell free scaffolds in a porcine model of retinitis pigmentosa did not cause inflammation, infection or local or systemic toxicity after one month. In addition, comprehensive ISO 10993 testing of photopolymerized scaffolds revealed a favorable biocompatibility profile. These results represent an important step towards understanding how two-photon polymerization can be applied to a wide range of biologically compatible chemistries for various biomedical applications.
Inherited retinal degenerative blindness results from the death of light sensing photoreceptor cells. To restore high-acuity vision a photoreceptor cell replacement strategy will likely be necessary. Unfortunately, single cell injection typically results in poor cell survival and integration post-transplantation. Polymeric biomaterial cell delivery scaffolds can be used to promote donor cell viability, control cellular polarity and increase packing density. A challenge faced in this endeavor has been developing methods suitable for generating scaffolds that can be used to deliver stem cell derived photoreceptors in an ordered columnar orientation (i.e., similar to that of the native retina). In this study we combined the biomaterial poly(caprolactone) with two-photon lithography to generate a biocompatible, clinically relevant scaffold suitable for retina cell delivery.
Huntington's disease (HD) is a devastating, progressive neurodegenerative disease with a distinct phenotype characterized by chorea and dystonia, incoordination, cognitive decline and behavioral ...difficulties. The precise mechanisms of HD progression are poorly understood; however, it is known that there is an expansion of the trinucleotide cytosine-adenine-guanine (CAG) repeat in the Huntingtin gene. Herein DI/LC-MS/MS was used to accurately identify and quantify 185 metabolites in post mortem frontal lobe and striatum from HD patients and healthy control cases. The findings link changes in energy metabolism and phospholipid metabolism to HD pathology and also demonstrate significant reductions in neurotransmitters. Further investigation into the oxidation of fatty acids and phospholipid metabolism in pre-clinical models of HD are clearly warranted for the identification of potential therapies. Additionally, panels of 5 metabolite biomarkers were identified in both the frontal lobe (AUC = 0.962 (95% CI: 0.85–1.00) and striatum (AUC = 0.988 (95% CI: 0.899–1.00). This could have clinical utility in more accessible biomatrices such as blood serum for the early detection of those entering the prodromal phase of the disease, when treatment is believed to be most effective. Further evaluation of these biomarker panels in human cohorts is justified to determine their clinical efficacy.
The factors affecting host-pathogen ecology in terms of the microbiome remain poorly studied. Chickens are a key source of protein with gut health heavily dependent on the complex microbiome which ...has key roles in nutrient assimilation and vitamin and amino acid biosynthesis. The chicken gut microbiome may be influenced by extrinsic production system parameters such as Placement Birds/m
(stocking density), feed type and additives. Such parameters, in addition to on-farm biosecurity may influence performance and also pathogenic bacterial numbers such as Campylobacter. In this study, three different production systems 'Normal' (N), 'Higher Welfare' (HW) and 'Omega-3 Higher Welfare' (O) were investigated in an industrial farm environment at day 7 and day 30 with a range of extrinsic parameters correlating performance with microbial dynamics and Campylobacter presence.
Our data identified production system N as significantly dissimilar from production systems HW and O when comparing the prevalence of genera. An increase in Placement Birds/m
density led to a decrease in environmental pressure influencing the microbial community structure. Prevalence of genera, such as Eisenbergiella within HW and O, and likewise Alistipes within N were representative. These genera have roles directly relating to energy metabolism, amino acid, nucleotide and short chain fatty acid (SCFA) utilisation. Thus, an association exists between consistent and differentiating parameters of the production systems that affect feed utilisation, leading to competitive exclusion of genera based on competition for nutrients and other factors. Campylobacter was identified within specific production system and presence was linked with the increased diversity and increased environmental pressure on microbial community structure. Addition of Omega-3 though did alter prevalence of specific genera, in our analysis did not differentiate itself from HW production system. However, Omega-3 was linked with a positive impact on weight gain.
Overall, our results show that microbial communities in different industrial production systems are deterministic in elucidating the underlying biological confounders, and these recommendations are transferable to farm practices and diet manipulation leading to improved performance and better intervention strategies against Campylobacter within the food chain. Video Abstract.
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