Academic literature on the topic 'Digestive system'

Piezo1, a non-selective cation channel directly activated by mechanical forces, is widely expressed in the digestive system and participates in biological functions physiologically and pathologically. In this review, we summarized the latest insights on Piezo1’s cellular effect across the entire digestive system, and discussed the role of Piezo1 in various aspects including ingestion and digestion, material metabolism, enteric nervous system, intestinal barrier, and inflammatory response within digestive system. The goal of this comprehensive review is to provide a solid foundation for future research about Piezo1 in digestive system physiologically and pathologically.

The aim of the research was to analyze the learning difficulties and alternative conceptions that Spanish pre-service teachers have about digestive physiology and anatomy. The study was conducted on a primary education bachelor’s degree biology course during the 2021/2022 academic year (n=91). The participants were asked to complete a conceptual test before (pre-test) and after the instruction (post-test). The results revealed that they had a limited knowledge of the digestive process before instruction (pre-test), especially those in the humanities baccalaureate group. Numerous alternative conceptions were identified, for example, that digestion ends in the stomach, mechanical digestion takes place only in the mouth, and nutrient absorption and transport into the bloodstream are not part of the digestive process. The results also indicated that levels of knowledge increased significantly after the course was completed (post-test); however, several features of the digestive process remained poorly understood, mainly because of the pre-service teachers’ lack of understanding of the cellular or molecular aspects that govern this process and their inability to distinguish between macro and micro levels of digestion. It is therefore recommended that the pre-service teachers acquire a comprehensive knowledge of the digestive by studying other scientific disciplines (physics, chemistry, cell and molecular biology, and so on).

Toxocariasis is common among children and causes digestive diseases. The aim of the work was to study the development of toxocariasis in children with digestive diseases. The serum levels of specific IgG to Toxocara canis and Ascaris, levels of IL-4 and TNF-α were determined in 63 children. In addition, tests for parasites and a retrospective survey in order to assess sanitation and hygiene practices were conducted. All children were divided into two groups: group I includes 19 (30.2%) patients seropositive for toxocariasis, and group II – 44 (69.8%) children without any parasites. The level of IL-4 was higher in group I (18.0 ± 6.4 pg/ml) than in group II (7.2 ± 2.0 pg/ml) (P < 0.001. While the level of TNF-α did not differ significantly between groups I (4.5 ± 2.1 pg/ml) and II (3.6 ± 1.1 pg/ml) (P > 0.05). A higher incidence of Toxocara was observed among rural residents (78.9%). Children with toxocariasis more often had soil-pica (42.1%), played with dogs (100%), and did not wash their hands (84.2%) compared to the group of uninfected children. It was noted that hygienic habits and place of living contribute to Toxocara canis infection. IL-4 levels were considerably higher in group I than in group II that can be accounted for the host immune response activation, at the same time, the levels of TNF-α did not differ. Children without toxocariasis had also increased levels of IL-4, which may be related to past helminthic infection. Keywords: children., digestive diseases, interleukin-4, toxocariasis, tumor necrosis factor - α

The main purpose of this article is to provide a detailed and concise explanation of the most common pathologies of the digestive system. This is composed of the digestive tract, liver, pancreas and gallbladder. Its main function is to carry out the digestion of food, to transform it into nutrients that the body uses as energy for its integral functioning, growth and cellular repair. The digestive system may present some diseases and disorders, both acute (short term) and chronic (long term). Among the latter, stomach and colorectal cancer represent a major public health problem.

ABSTRACT A study was conducted to develop a traditional system at Syhifa Medika Public Clinic to overcome the lack of information and time-consuming queues at the clinic, so that people can check their digestive system conditions more easily and efficiently. The developed expert system for diagnosing digestive diseases in humans has succeeded in helping many local people in finding information on digestive diseases and providing time efficiency that is useful for people who live far from the clinic. Therefore, the expert system for diagnosing digestive diseases in humans can be a very useful alternative to improve the current health system. Keywords: Expert System, Digestion, Digestive Disease, Certainty Factor, Web

Although omnivores are able to alter the structure and functions of their digestive system in response to changes in dietary carbohydrate content, it is unclear whether carnivores are capable of such adaptive flexibility. Hence we recorded growth rates, intestinal morphometrics and histology, and nutrient uptake rates and concentrations of disaccharidases in the intestines of a carnivorous fish, the rainbow trout, fed different levels and types of carbohydrate. The trout is unable to adaptively regulate digestive system structure and function to increase glucose availability in response to increasing levels of dietary carbohydrates, even to easily digestible forms such as glucose. Paradoxically, a reduction in the concentrations of enzymes associated with carbohydrate digestion in response to elevated levels of easily digested carbohydrates suggests that carnivores may actually try to repress carbohydrate digestion when glucose is available in high quantities. Thus the lower levels of carbohydrate in the diet of trout throughout their evolution has resulted in a reduced ability to phenotypically regulate the digestion of carbohydrates.

The aim of this study is to determine the students’ misconceptions about the digestive system. In this quantitative research, the study group comprised totally 259 sixth-, seventh-, and eighth-grade students. The data were collected through a three-tier diagnostic test and analyzed in terms of scientific knowledge, the lucky guess, lack of knowledge, and misconception levels of students on digestive system. According to the findings, 20.1% of the students’ answers were in the scientific knowledge category and 9.1% were in the lucky guess category. On the other hand, 39.7% of the answers were in the lack of knowledge category and 26.0% were in the misconception category. The most prominent findings in the study were the students’ misconceptions in a few questions, especially about physical and chemical digestion. In addition, some students did not fully understand the distinction between the excretory and digestive organs and the functions of some accessory. They also gave incorrect answers about the organs where the digestion of proteins, carbohydrates and fats begins and ends. At the end of the study, suggestions were made to eliminate the misconceptions.

Este trabalho consiste em um estudo detalhado do sistema digestivo de Phibalosoma phyllinum (Phasmida, Phasmatidae) num enfoque morfofuncional. Do ponto de vista anatômico, o seu sistema digestivo é constituído por um intestino anterior, um intestino médio e um intestino posterior. O intestino anterior é composto por uma cavidade bucal (onde se abre o ducto da glândula salivar bilobada), uma faringe, que se continua para o esôfago, terminando em um proventrículo, que forma uma válvula em seu interior. O intestino médio é formado por um ventrículo tubular, dividido em três regiões: ventrículo anterior (VA), ventrículo médio (VM) e ventrículo posterior (VP). Este último foi, ainda, subdividido em proximal (VPI) e distal (VPII). Na região do VPI, foi constatada a presença de estruturas denominadas de apêndices ventriculares, formadas por protuberâncias, que se inserem no tubo digestivo, e canalículos, que se projetam da região apical de cada uma delas e terminam em fundo cego. O intestino posterior é dividido em um íleo e um reto que termina no ânus. A análise histológica mostrou que o intestino anterior é formado por um epitélio simples, composto por células pavimentosas, revestido por uma cutícula, que se modifica na forma de pequenas espículas ao longo desta região. O proventriculo é composto por uma válvula muscular simples, que separa o intestino anterior e o intestino médio. Este último é formado por um epitélio simples, constituído por células do tipo colunar, chamadas de enterócitos, principais responsáveis pela secreção de enzimas digestivas e pela absorção dos nutrientes, por células regenerativas, que se apresentam reunidas em ninhos na base do epitélio, e por células endócrinas. Os apêndices ventriculares, por sua vez, possuem um epitélio simples e contínuo com o epitélio ventricular. As células das protuberâncias apresentam-se grandes e arredondadas, enquanto que os canalículos são compostos por um epitélio de células achatadas, semelhante ao dos túbulos de Malpighi. Na região de transição entre o epitélio ventricular e o intestino posterior se inserem os túbulos de Malpighi. O epitélio do intestino posterior é do tipo cúbico, simples, revestido por cutícula. A luz do intestino médio (ou ventrículo) é revestida por uma estrutura tubular, denominada de membrana peritrófica, cuja existência foi comprovada por microscopia de fluorescência com a utilização da técnica WGA-FITC (aglutinina do gérmen do trigo conjugada à fluoresceína). Com a finalidade de identificar regiões específicas do ventrículo onde ocorre a absorção ou secreção de água através do epitélio, foram realizados experimentos fisiológicos de ingestão e injeção do corante amaranto em solução. Verificou-se que, quando o corante é ingerido pelos insetos, o VA apresenta-se corado, tanto em animais em jejum quanto alimentados, indicando ser este o possível sítio de absorção de água no ventrículo. Por sua vez, a partir de experimentos com a injeção do mesmo corante na hemolinfa, foi constatada a sua tomada pelos túbulos de Malpighi, indicando serem estes os principais sítios de tomada de água da hemolinfa e de sua secreção para a luz do tubo digestivo. Tanto em animais em jejum, quanto alimentados, o corante injetado é encontrado na luz do intestino posterior. Entretanto, nos animais em jejum, o corante é capaz de se difundir, também, pelo ventrículo até a sua região anterior. A análise ultraestrutural do intestino médio revelou que a superfície apical dos enterócitos constituintes apresenta-se modificada na forma de microvilosidades. Nas membranas laterais, observam-se especializações juncionais na forma de desmossomos apicais, seguidos por junções septadas lisas. A membrana plasmática basal, por sua vez, exibe diversas invaginações, formando uma rede complexa de canais com mitocôndrias associadas. Nas células do VA e VM, essa rede exibe um número limitado de aberturas para a lâmina basal, o que indica um maior potencial de absorção de água pelo epitélio ventricular, a partir de sua luz. Nas células da região do VP, o número de aberturas é bem maior, o que sugere que pode ocorrer secreção de água e íons através desta região, não detectável nos experimentos com corantes. Por outro lado, as células regenerativas exibem características típicas de células indiferenciadas, com núcleo grande e poucas organelas. Células endócrinas, por sua vez, são, eventualmente, detectadas na base do epitélio, sem se prolongarem até a superfície apical do epitélio. Foi observado, ainda, que tanto os canalículos ventriculares, quanto os túbulos de Malpighi são formados por células achatadas, com microvilosidades apicais modificadas portando mitocôndrias em seu interior e membrana plasmática basal formando um labirinto complexo, com muitas aberturas para a lâmina basal e com muitas mitocôndrias associadas. Com relação a atividade secretora do epitélio ventricular, verifica-se a existência de grandes quantidades de retículo endoplasmático rugoso e diversas áreas de Golgi concentradas, principalmente, no citoplasma perinuclear. Nas regiões VA e VM, é detectado um grande número de vesículas secretoras, cujo mecanismo de secreção parece ser o merócrino. Ao longo de todo VP, por outro lado, vesículas secretoras estão, aparentemente, ausentes no citoplasma apical, mas pode ser constatada a presença de dilatações nas microvilosidades, algumas das quais apresentem pequenas vesículas em seu interior. Esta observação é sugestiva da ocorrência de secreção do tipo microapócrina nesta região. Devem ocorrer, portanto, dois mecanismos de secreção diferentes ao longo do ventrículo de P. phyllinum: o merócrino (no VA e no VM) e o microapócrino (no VP) O local de produção e secreção das enzimas amilase e tripsina pôde ser localizado através de experimentos de imunomarcação ultraestrutural com a utilização de anticorpos heterólogos. Ambas as enzimas foram detectadas na região do VA e do VM, podendo ser traçadas nas áreas de Golgi, nas vesículas secretoras e na luz do epitélio, junto às microvilosidades, seguindo, pois, a rota secretora. Ambas as enzimas foram identificadas no interior do mesmo tipo de vesículas de secreção, indicando que devem ser eliminadas conjuntamente através da mesma via secretora. Medidas de pH luminal revelaram grandes diferenças de pH ao longo do tubo digestivo nesta espécie. Enquanto que na região anterior o pH é mais ácido (5,3 no intestino anterior e 5,6 no VA), ele vai se tornando mais alcalino nas regiões mais posteriores do ventrículo (6,3 no VM anterior, 8,0 no VM posterior, 9,1 no VPI e 8,5 no VPII) e é neutro no intestino posterior (7,3). Foi determinado, ainda, o efeito do pH sobre a atividade das enzimas tripsina e amilase. A maior atividade para tripsina foi observada no pH 9,0. Já para amilase, a maior atividade foi observada em pH 5,0. No que diz respeito a atividade de enzimas digestivas, ficou evidente que a atividade de amilase e tripsina se concentra no conteúdo do intestino anterior e VA.
This work presents a detailed morphofunctional study of the digestive system of Phibalosoma phyllinum (Phasmida, Phasmatidae). From an anatomical point of view, the digestive system of this insect is formed by a foregut, a midgut and a hindgut. The foregut is composed by the buccal cavity (where the salivary gland\'s duct open), a pharynx and an aesophagus that ends in the proventriculus. The midgut consists of a tubular ventriculus and it can be divided in three regions: the anterior ventriculus (AV), the middle ventriculus (MV), and the posterior ventriculus (PV) which can be further subdivided in its proximal (PVI), and distal (PVII) sub-regions. The presence of a complex system of ventricular appendices was observed in the PVI sub-region, which are formed by protuberances, in the external ventricular surface, and by blind-ended canaliculi, which are connected to the protuberances. The hindgut is divided into an ileum and a rectum that ends in the anus. Seen by light microscopy, the foregut is made up by a simple epithelium, which is composed of squamous cells and covered by a cuticle layer. Through the whole foregut the cuticle forms spines. The proventriculus is formed by a simple muscular valve that separates the foregut from the midgut. The midgut itself is formed by a simple epithelium, which is made up of three different cell types: columnar cells (enterocytes), which are the main site of enzyme production and secretion, and nutrient absorption, the regenerative cells, which are clustered in nidi at the basal portion of the epithelium, and the endocrine cells. The ventricular appendices, in turn, are formed by a simple epithelium that is continuous with the ventricular epithelium. Cells from the protuberances are large showing a round shape, while canalicular cells are short, and very similar to the ones presented in the Malpighian tubules. In the transition between the midgut and the hindgut, several Malpighian tubes branch off. The hindgut is formed by a simple epithelium, lined by cuticle. The ventricular lumen is covered by a tubular structure called peritrophic membrane whose presence was confirmed by fluorescence microscopy, using chitin-binding lectin WGA (wheat germ agglutinin) coupled with FITC (fluorescein isothiocyanate). In order to identify specific ventricular regions where water absorption and secretion through the epithelium take place, physiological experiments, using amaranth dye solution were performed. This solution was either orally administered, or injected in the hemolinph of both fed and starved insects. These experiments revealed that, both in fed and starved animals, the AV is the main site of water absorption, whereas the Malpighian tubules are the main sites of water secretion into the ventricular lumen. Ultrastructural analysis showed that enterocytes present an apical surface modified into well-developed microvilli. In their lateral surface, the adjacent plasma membranes are linked by desmosomes and smooth septate junctions. The basal plasma membrane shows several infoldings, forming a labyrinth of channels with associated mitochondria. In the AV and MV, these infoldings present a limited number of openings to the basal lamina, which indicates a greater water absorption potential of these regions from the gut lumen. In the PV cells, the number of openings is greater, indicating that these regions may be involved in water secretion (although occurring in levels that are undetectable through dye experiments). Regenerative cells nidi, in turn, can be observed in the basal portion of the epithelium throughout the midgut. This cell type shows characteristics of undifferentiated cells, such as large nuclei and few organelles. Endocrine cells are confined to the basal portion of the epithelium. Both the ventricular canaliculi and the Malpighian tubules are made up by cuboidal cells with modified apical microvilli bearing mitochondria in their interior, and basal plasma membrane forming a labirinth with many well developed infolds and openings to the basal lamina, as well as many associated mitochondria. An intense secretory activity was observed along the entire midgut. Large amounts of rough endoplasmic reticulum, well developed Golgi areas were observed in the enterocytes. In the AV and MV a large number of secretory vesicles could be observed concentrated in the apical portion of the cells, and their contents are probably eliminated by a merocrine mechanism. Along the PV, secretory vesicles are apparently absent but microvilli display dilated tips frequently showing small vesicles in their interior. This observation may indicate the occurrence of a microapocrine secretory mechanism in this ventricular region. The enzymes amylase and trypsin were immunolocalized in the cells from the AV and MV. In these regions, the two enzymes were detected in Golgi areas, secretory vesicles and in the the ventricular lumen, between the microvilli. Thus, both enzymes seem to be produced and eliminated through the same secretory pathway. Luminal pH measurements revealed a great variation of the pH along the intestine of this species. While in its anterior region the pH is acid (5,3 in the foregut and 5,6 in the AV), it becomes gradually alkaline towards the posterior regions (6,3 in the anterior MV, 8,0 in the posterior MV, 9,1 in the PVI and 8,5 in the PVII); in the hindgut the pH is neutral (7,3). The effect of the pH on amylase and trypsin activities was also measured. It was determined that trypsin\'s optimal pH was 9,0, and amylase\'s optimal pH was 5,0. Biochemical assays of digestive enzymes revealed the presence of amylase and trypsin in the luminal contents, mainly in the foregut and AV. In spite of that, it is possible that trypsin\'s activity is greater in the MV and PV, where the alkaline luminal pH matches the optimal pH for this enzyme. Chymotrypsin is also present in the lumen of the foregut and AV, but, unlike amylase and trypsin, its major activity is found in the AV. Aminopeptidase is found in the ventricular epithelium, mainly in the MV and PV, and maltase is detected associated with the microvillar glicocalix in the AV and PV regions. The hindgut showed low levels of digestive enzyme excretion, both in fed and starved animals, suggesting that these enzymes are recovered during the digestive process. Thus, these results point to the occurrence of an endo-ectoperitrophic circulation of digestive enzymes in both fed and starved animals, in which the AV is the main absorption site of water and the Malpighian tubules, the main secretion site. Initial carbohydrates digestion should occur in the foregut and in the AV, in the endoperitrophic space, whereas its final digestion should take place in the epithelial surface. Protein digestion should take place in the MV and in the PV; initial digestion should occur in the luminal endoperitrophic space, whereas final digestion takes place in the epithelial surface of these regions. Carbonic anhydrase assays revealed a high activity of this enzyme in the ventricular appendices. This fact, along with the morphological similarity between ventricular canaliculi and Malpighian tubules suggest that the canaliculi and the Malpighian tubules are homologous structures. Along the evolutionary process, the canaliculi probably acquired the capability to promote the alkalization of the PV lumen (mainly in the PVI region) thus affecting the digestive process

O mosquito Aedes aegypti é vetor de doenças como a febre amarela, dengue, chinkungunya e zika. O sistema digestório é responsável pela digestão e absorção de nutrientes, é também uma interface com o ambiente externo sendo a porta de entrada de organismos infecciosos. A presença de duas lipases digestivas foi confirmada por qPCR, uma na fase larval (L-Aa7051) e outra na fase adulta (L-Aa7055). Estas enzimas foram agrupadas na família das lipases neutras e apresentam alterações em resíduos envolvidos na especificidade, domínio tampa e alça β9. A L-Aa7055 recombinante foi expressa heterologamente em Escherichia coli na porção insolúvel, com atividade após a renaturação. Observamos que a expressão da lipase L-Aa7055 sofre uma redução de 30% na infecção Plasmodium gallinaceum, não sendo afetada pelo vírus dengue sorotipo 2 (DENV2). A digestão de lipídeos é importante na fase larval, com altos níveis de transcrito. Um estudo mais aprofundado ainda será necessário para compreender completamente o papel das lipases no processo infeccioso.
The Aedes aegypti borne diseases yellow fever, dengue fever, chinkungunya and zica are important public healthy problems. The digestion and absorption of nutrients are performed in the digestive system, which is also an external environment interface that allows the infection by pathogenic microorganisms. The presence of two digestive lipases were identified by qPCR, L-Aa7051 in the larval phase and L-Aa7055 in the adult female. The lipase sequences were grouped in the neutral family, and exhibit alterations in residues involved in specificity, lid domain and β9 loop. The recombinant L-Aa7055 was expressed in the insoluble fraction, and show activity after a renaturation process. We notice that the expression levels of L-Aa7055 are reduced by 30% in the Plasmodium gallinaceum infection and were not affected by serotype 2 dengue virus (DENV2). The lipid digestion is important in the larval phase, with higher transcript levels. New studies will be necessary to the complete understanding of lipase contribution in the infectious process.

Cten (also known as Tensin4) is the fourth member of the Tensin gene family. It lacks the N terminal actin binding domain while retaining the C terminal SH2 and PTB domains. This helps to bind Cten to the intracytoplasmic tail of β1 integrin and puts it at the heart of focal adhesions. It is reported to be a tumour suppressor in kidney and prostate cancer where normal tissues show high expression. However in a number of tumours, including colorectal cancer, Cten has been labelled as an oncogene. Cten which normally is a cytoplasmic protein gives nuclear staining in colorectal metastatic deposits. It increases motility, invasion and colony formation in colorectal cancer cells. In this study we have tried toexplore the mechanism of functional activity and regulation of Cten. We looked at Cten in the nucleus in vitro and identified new downstream binding targets. In addition we investigated the role of the SH2 domain of Cten concentrating on its downstream signalling molecules and binding partners. Furthermore, we explored regulators of Cten. In this study we have forced nuclear localisation of Cten by tagging it with a nuclear localisation sequence (NLS) and found a significant increase in cell motility. In order to investigate the SH2 domain we used site directed mutagenesis to change potentially important amino acids namely Arginine at 474 to Alanine (R474A), which is important for binding tyrosine phosphorylated proteins. Moreover, we displayed that Cten underwent tyrosine phosphorylation and additionally changed three tyrosine residues i.e. Y449F, Y479F and Y530F via site directed mutagenesis. We found R474 and Y479 to be important in regulating cell motility and that known downstream targets such as ILK and FAK are dependent on an intact SH2 domain. Furthermore we have identified Cten to be physically bound to FAK in the cytoplasm and nucleus and new downstream targets identified such as Src and Paxillin. Regarding possible regulators of Cten, we found that Cten might be a possible substrate for calpain. Another regulator considered was CD24 due to its role in movement of integrins into lipid rafts and we found it was a positive regulator of Cten. In conclusion localisation of Cten into the nucleus causes an augmentation of its motility enhancing functions. Cten regulates cell motility via its SH2 domain. Arginine 474 and Tyrosine 479 are important for its function. Cten regulates levels of ILK, FAK, Src and Paxillin through its SH2 domain and binds to FAK in both cytoplasm and nucleus. Calpain and CD24 were found to possible regulators of Cten in colorectal cancer. Future studies are needed to define its role in signalling at focal adhesions and these studies should be validated in other cancer cell models as well to establish Cten as regulator of cell motility in cancer.

Cystic fibrosis (CF) is one of the commonest life-limiting genetic disorders in the Caucasian population. Management involves frequent administration of antibiotics including aminoglycosides. With improving survival, it is time to focus on various age-related and treatment-associated adverse influences. The objective of this research was to evaluate renal function in CF, determine the effects of cumulative antibiotic exposure and to identify ways to reduce associated comorbidity. A cross-sectional study showed that a small number of adults and children with CF had low glomerular filtration rate (GFR), and there was no association between GFR and cumulative antibiotic exposure. An above normal GFR was identified in one in four children with CF. Estimated GFR calculated by creatinine-based equations did not accurately predict the GFR measured by the gold standard 51Cr-EDTA (51chromium-ethylenediamine tetraacetic Acid). Pure tone audiograms identified a raised hearing threshold in one in four people with CF, which did not correlate with increasing aminoglycoside exposure. A randomised controlled study established that there is no difference in the pharmacokinetics of tobramycin when administered intravenously in the morning or evening. A Cochrane systematic review concluded that there was insufficient evidence to support a routine use of bronchoalveolar lavage in the management of pulmonary infections with Pseudomonas aeruginosa in children with CF below 5 years old. CF gene (Cystic Fibrosis Transmembrane Conductance Regulator, CFTR) is expressed in pig kidneys. Histological and molecular experiments established that there is no difference between the newborn pigs with genotypes CFTR -/- (knockout) and CFTR +/- (heterozygous) or CFTR +/+ (wild-type) pig kidneys in the renal morphology and in the expression of various renal endocytic receptor proteins. The vascular haemodynamic parameter, augmentation index ascertained in a small group of children with CF suggests a possibility that the vascular age may be advanced in people with CF right from their childhood. In summary, these studies have established a low prevalence of renal disease in CF and a lack of association between cumulative antibiotic exposure and GFR. Further research is needed to evaluate the natural history of high GFR in paediatric CF population. Kidneys from pig model of CF may provide an alternative model to investigate the renal disease in CF.

CD24 is a small (81 amino acids) GPI anchored protein which is involved in promoting cell motility and stemness and may be a part of the metastatic process. It is a heavily glycosylated molecule and contains numerous O-glycosylation sites together with two N-glycosylation sites. N-glycosylation is thought to be important in protein function, and therefore, the aim of this study is to (a) investigate the importance of N-glycosylation in the function of CD24, (b) identify other potentially functional sites in CD24 by deletion mapping, (c) define downstream targets of CD24, and (d) identify the extrinsic signals of which activate CD24. (a) Through site-directed mutagenesis, we changed the glycosylated residues N32 (ACC to CAA) and Q52 (AAT to CAG) in CD24. Mutating each of these sites individually, when compared to pCCD24WT (wild-type CD24), caused a partial reduction in ability to induce cell motility and cell invasion (cell motility p=0.0001 cell invasion p=0.0001) and, unexpectedly, resulted in significantly enhanced cell proliferation (p=0.0001). Mutation of both sites resulted in a near loss of motility induction and retained cell proliferation. (b) We mapped the functional sites of CD24 by deleting seven amino acid segments of the whole of the mature peptide. Apart from the N-glycosylation sites, no other functional domains were identified which altered cell motility or proliferation. (c) Previously, in our lab it has been shown that Cten is downstream motility-inducing target of CD24. We hypothesised that CD24 may signal through the Notch pathway since Notch1 has an important role in maintaining CSCs. Results showed that forced expression of CD24 upregulates Notch1 and Cten whilst knockdown of CD24 causes loss of Notch1 and Cten expression. However, forced expression of CD24 with simultaneous knockdown of Notch1 resulted in failure to induce Cten. (d) CD24 is reported to act as a ligand of P-selectin. We found that stimulating CD24 expressing cell lines induced with P-selectin induced cell motility (p=0.0011) and caused an increased in the protein expression of downstream targets of CD24. Stimulating cell lines expressing CD24 with mutant glycosylation sites resulted in a failure to induce motility or CD24 targets. We conclude, the removal of the N-glycosylation sites in CD24 resulted in a loss of cell migration and invasion, thereby suggesting the importance of these sites in mediating the migration and invasion functions of CD24. Unexpectedly, these mutations also appeared to stimulate cell proliferation, suggesting that wild type CD24 can functionally inhibit cell proliferation. Deletion mapping did not reveal any other functional sites on the mature CD24 suggesting that O-glycosylation is relatively affecting the glycosylation in the biology of CD24. Notch1 was to be an important downstream target of CD24 and a regulator of Cten. The binding of P-selectin with CD24 resulted in increased motility of CD24 which is also dependent on N-glycosylation.

In health, the gut provides a barrier between the external and internal environment. This selectively permeable barrier allows absorption of nutrients and water from the gastrointestinal contents, whilst preventing the transfer of noxious material such as bacteria. During episodes of inflammation, this barrier becomes compromised, allowing transfer of noxious material into the systemic circulation, leading to disease states such as inflammatory bowel disease and septic shock. There are no clinically available compounds to combat this increase in permeability directly. The endocannabinoid system is a group of endogenous lipid signalling molecules which activate membrane-bound receptors. Plant-derived and synthetic compounds also act at these receptors, generating a wide variety of secondary effects. The aims of this study were to identify compounds with action on the endocannabinoid system which could be used clinically to treat inflammation and hyperpermeability of the gastrointestinal tract, exploring mechanisms of action. Systematic review and meta-analysis of existing literature revealed 51 preclinical studies, and 2 clinical studies examining the effect of cannabinoid compounds. In preclinical studies, cannabinoid drugs reduced myeloperoxidase activity in the gastrointestinal mucosa within mouse and rodent models of colitis (standard mean difference -1.26, 95% confidence interval (CI)-1.54 to -0.97, I2=48.1%) and macroscopic disease activity scores (standard mean difference -1.36, 95% CI -1.62 to -1.09, I2=61%). Clinical trials found no overall benefit of cannabinoid drugs in Crohn’s disease (mean difference -74.97, 95% CI –229 to 0.79, I2=75%). Two compounds, cannabidiol and palmitoylethanolamide, possessing positive outcomes and preferable side effect profiles, were put forward for further study to examine potential clinical benefit. The mechanism of action of palmitoylethanolamide and cannabidiol were explored further by examination of their effects on the immune response, permeability of cultured cell monolayers, intracellular signalling pathways, expression of membrane-bound proteins governing permeability and receptors of the cannabinoid system. We found that these agents were anti-inflammatory in both cultured Caco-2 cells and explant human colonic tissue, prevented increases in permeability secondary to inflammation, and were likely to act through adenylyl cyclase, protein kinase A and extracellular signal-regulated kinases. The downstream effects of these compounds prevented down-regulation of the TRPV1 receptor, upregulation of aquaporin 3 expression, and prevention of downregulation of claudin-3. The effects of palmitoylethanolamide and cannabidiol were then examined on permeability in the human colon in vivo by means of a double blinded, randomised controlled trial. This study demonstrated that aspirin increased the permeability of the human gut, determined by increases in urinary concentrations of lactulose and D-mannitol, quantified by mass spectrometry. Groups receiving oral cannabidiol or palmitoylethanolamide demonstrated lower urinary concentrations of lactulose and D-mannitol, suggesting that these two drugs could be used clinically to prevent disease-induced hyperpermeability. In conclusion, cannabidiol and palmitoylethanolamide have shown consistent anti-inflammatory actions in colonic ex vivo and in vitro models, and also prevented increases in intestinal permeability in vitro and also in vivo in a randomised, double blind, placebo-controlled trial. Their clinical use in IBD should now be assessed in phase II clinical trials.

C-terminal tensin-like (Cten, also known as Tensin4) is the member of the tensin gene family. Cten functions as an oncogene in a variety of cancer types and its expression is commonly associated with poor prognosis and metastasis in colorectal cancer (CRC). Although several studies have shown that Cten has a critical role in the regulation of cell motility and invasion in different tumour tissues, the underlying signalling mechanisms have not been fully elucidated. This thesis investigated the biological activity of Cten in four different ways in order to further elucidate the mechanisms of Cten signalling in CRC cells. Potential downstream targets of Cten signalling involved in the regulation of epithelial-to-mesenchymal transition (EMT) induced cell motility i.e. Rho-associated protein kinase1 (ROCK1), Src and Snail were investigated. Cten expression was manipulated in different cell lines using multiple approaches including forced expression, gene knockdown and constitutive depletion (through Crispr/Cas9 gene deletion) to eliminate artefacts of methodology and cell line specific effects. Snail, Src and ROCK1 were identified as novel downstream targets of Cten signalling and additionally, Cten was shown to increase the stabilisation of both Src and Snail proteins. The functional relevance of Cten-Snail, Cten-Src and Cten-ROCK1 signalling was assessed, and the overall findings demonstrated that Cten could promote cell motility and colony formation directly through the positive regulation of the Src/ROCK1/Snail dependent axis. To gain a deeper insight into the mechanisms of Cten’s biological function, mutations, at two important residues (i.e. arginine 474 and tyrosine 479) in the Src homology 2 (SH2) domain of Cten were introduced into one construct (GFP-CtenR474A+Y479F) using site directed mutagenesis. These two residues in the SH2 domain of Cten were found to not only be important for interacting with Src, ROCK1, or Snail signalling, but also for regulating cell motility and colony formation efficiency. Numerous Cten regulatory factors have been identified, however, little is known about how Cten is activated and regulated in cancer cells. The relationship between transforming growth factor beta 1 (TGFβ1) and Cten was investigated and stimulation of cells with TGFβ1 or knockdown of TGFβ1 resulted in changes in Cten expression as well as its downstream targets of ROCK1, Src, Snail, and N-cadherin. Furthermore, this positive interaction between TGFβ1 and Cten was functionally relevant and caused changes in cell motility. and the nuclear translocation of ROCK1, Src, and Snail protein increased by TGFβ1 is probably mediated via upregulation of the Cten signalling pathway The biological function of Cten in the nucleus was further investigated and shown to increase nuclear localisation of Src, ROCK1, and Snail, further promoting the migratory capability and colony formation efficiency in CRC cells. Finally, Cten expression was shown to positively correlate with both ROCK1 and Src expression in a series of primary CRCs. This correlation was consistent with that observed following manipulation of Cten expression in CRC cell lines. In conclusion, this study has revealed a number of novel findings regarding the biological function of Cten signalling in CRC. However, further validation of the findings may enhance the understanding of the role of Cten in the invasion-metastasis cascade in the future.

The goal this reviews was to determined the influence of the diet on digestive system in the birds and roles of digestive tract. Birds have a very complex digestive system, which is thought to have a significant impact on how well they utilize the nutrition that they consume. It is expected that the stomach, intestines, cecum, proventriculus, and gizzard of herbivorous birds will be larger than those of carnivorous birds, whereas herbivorous birds tend to have longer, more complex digestive tracts. This may be due to herbivorous require high time and energy to the breakdown of cellulose. Their digestive processes were described for birds with different diets.. The proventriculus' size impacted by the diet, not the intestines, gizzard, or cecum. Insectivores had the largest proventriculi, whereas herbivores had the smallest, and omnivores had a proventriculus of a medium size. The function of the avian digestive organs in regulating the gut bacteria, fermenting unabsorbed nutrients, recycling nitrogen from urine, and maintaining gut health. Through aiding food uptake, and interactions with the immune system, gastrointestinal microbiota play a crucial role in maintaining organism health. Only tiny and/or soluble particles, along with digestive juices and urine, will reflux into the caeca due to anatomical and physiological adaptations. Salts and water will be reabsorbed here, and the rich bacteria will ferment uric acid and carbohydrates into ammonia and volatile fatty acids. The caeca may thereby affect the bird's nutritional health. Starch and proteins can be consumed, stored, and partially digested in the early section of the avian digestive system. With the exception of the absence of lacteals, the avian gut has a comparable anatomy to other monogastric animals. The microvilli in the avian intestine are covered by a noticeable glycocalyx. The mammalian liver's actual lobular structure is absent from the avian liver. Around the bile caniculi, hepatocytes are organized in plates two layers thick of cells. Acinar cells, that produce digesting enzymes to the pancreatic ducts, endocrine cells, that secrete hormones to the bloodstream, are found in the two main lobes and two smaller lobes of the avian pancreatic structure. The colon structure is similar to that of intestine except the poor enervation.

Diverticulosis occurs when small, bulging pouches (diverticula) develop in your digestive tract. When one or more of these pouches become inflamed or infected, the condition is called diverticulitis. Diverticula are small, bulging pouches that can form in the lining of your digestive system, although it was rare before the 20th century, diverticular disease is now one of the most common health problems in the western world. It’s a group of conditions that can affect your digestive tract. The most serious type of diverticular disease is diverticulitis. It can cause uncomfortable symptoms and, in some cases, serious complications. If left untreated, these complications can cause long-term health problems. Read on to learn more about diverticulitis, including its causes, symptoms, treatment options, and how your diet might affect your risk of developing it. Objective: In this paper, our main focus was on diverticulitis and surgical intervention, and only relevant studies were discussed. Methodology: PubMed database was used for articles selection, and papers on diverticulitis were obtained and reviewed. Conclusion: Colonoscopy is best avoided in acute and uncomplicated diverticulitis. Classically, it is a surgical disease but uncomplicated cases can often be managed conservatively. Follow up of treated diverticulitis occurs after four weeks via colonoscopy, in selected cases assessing the risk of developing colonic cancer. Novel therapies are under-studied and are probable replacements for surgical intervention.

Review question / Objective: Is probiotic therapy as effective or more effective than existing treatments in relieving the severity of constipation and improving the patient's mental status and quality of life in elderly patients with constipation? Do probiotic treatments pose greater risks than existing treatments for older patients with constipation? Condition being studied: Constipation is a common digestive disorder with a worldwide prevalence of 14-30%, and the prevalence increases with age. Constipation seriously impairs patients' quality of life, leads to significant medical costs, and places a burden on the healthcare system. For constipation, Western medicine uses lifestyle changes, medication, psychotherapy, biofeedback, and surgery to treat the condition.

To increase our food security in Västerbotten we will need to become more self-sufficient of both energy, feed and nutrients that are now imported to the region. Biogas production from different waste streams is one solution to this. Biogas is produced using biowaste or sewage sludge as substrate in the major cities Umeå and Skellefteå. Biogas systems offer a range of benefits to society. Biogas production is currently prized for its climate benefits when replacing fossil fuels for the production of heat, electricity and vehicle gas, but at Bothnia Nutrient Recycling we have studied how to use the digestate, i.e. the residual product of production, as fertilizer in agriculture. We have been working to improve profitability for biogas producers and develop sustainable products from recycled nutrients, like phosphorus and nitrogen. Improving the uses for digestate increases self-sufficiency in agriculture and contributes to a circular economy. We conducted three agricultural demonstration experiments in collaboration with agricultural high schools in Finland and Sweden to introduce digestate and digestate products to the future farmers in the regions. We found that it may be possible to replace cattle slurry with compost when growing maize despite the low levels of nitrogen, N, available to plants in the compost. In barley, NPK fertilizers gave the highest yield. Digestate from HEMAB and sludge biochar supplemented with recycled ammonium sulphate gave a smaller yield but higher than unfertilized crop. Digestate from a dry digestion biogas plant in Härnösand was better suited to barley than to grass because in an experiment on grass ley the viscous fertilizer did not penetrate the grass and did not increase the growth of the grass. Fertilizer effects on crop quality were small. There was no increased uptake of heavy metals in barley after fertilization with digestate or digestate products compared to NPK fertilization. These demonstration experiments show that more thorough scientific experimentation is needed as a foundation for recommendations to farmers. The amounts of nitrogen and phosphorous in digestate from Västerbotten that could become used as fertilizer were modelled. It showed that if sewage sludge digestate is used to make sludge biochar and ammonium sulphate and the other available digestates are used directly in agriculture, the entire phosphorous demand but only a small part of the nitrogen demand in the county, could be covered. Thus, to achieve a true circular food production, development and increase of both the waste handling sector and agriculture is needed.

Review question / Objective: Do patients with inflammatory bowel disease and treated with any anti-TNFα drug who had the HLA-DQA1*05 allele (in heterozygosis or homozygosis) have lower response or persistence to those drugs than patients without HLA-DQA1*05 allele? Condition being studied: Inflammatory bowel diseases (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition that may affect any part of the digestive tract (CD) or be limited to the colon (UC). While the specific aetiology of IBD remains unknown, it is believed to involve a complex impairment in the immunity of the gut mucosa due to a combination of several genetic and environmental factors, being the microbiota one of the latest that more attraction has received in recent years. Symptoms of IBD (such as abdominal pain, diarrhoea, fever, tiredness or rectal bleeding) may be either constant or alternate between periods of limited disease activity and flares with remarkable presence of symptoms. As IBD is associated with significant morbidity and disability, pharmacological treatment is required in most cases, especially in CD, aimed at reducing the inflammatory response and attenuating the activity of the immune system. In the moderate and severe forms of the disease, therapy is usually based on immunosuppressant and/or biological drugs. Among the latest, anti-TNFα drugs (infliximab or adalimumab) are normally chosen as the initial biological therapy.

Recent concerns regarding global warming and energy security have accelerated research and developmental efforts to produce biofuels from agricultural and forestry residues, and energy crops. Anaerobic digestion is a promising process for producing biogas-biofuel from biomass feedstocks. However, there is a need for new reactor designs and operating considerations to process fibrous biomass feedstocks. In this research project, the multiphase flow behavior of biomass particles was investigated. The objective was accomplished through both simulation and experimentation. The simulations included both particle-level and bulk flow simulations. Successful computational fluid dynamics (CFD) simulation of multiphase flow in the digester is dependent on the accuracy of constitutive models which describe (1) the particle phase stress due to particle interactions, (2) the particle phase dissipation due to inelastic interactions between particles and (3) the drag force between the fibres and the digester fluid. Discrete Element Method (DEM) simulations of Homogeneous Cooling Systems (HCS) were used to develop a particle phase dissipation rate model for non-spherical particle systems that was incorporated in a two-fluid CFDmultiphase flow model framework. Two types of frictionless, elongated particle models were compared in the HCS simulations: glued-sphere and true cylinder. A new model for drag for elongated fibres was developed which depends on Reynolds number, solids fraction, and fibre aspect ratio. Schulze shear test results could be used to calibrate particle-particle friction for DEM simulations. Several experimental measurements were taken for biomass particles like olive pulp, orange peels, wheat straw, semolina, and wheat grains. Using a compression tester, the breakage force, breakage energy, yield force, elastic stiffness and Young’s modulus were measured. Measurements were made in a shear tester to determine unconfined yield stress, major principal stress, effective angle of internal friction and internal friction angle. A liquid fludized bed system was used to determine critical velocity of fluidization for these materials. Transport measurements for pneumatic conveying were also assessed. Anaerobic digestion experiments were conducted using orange peel waste, olive pulp and wheat straw. Orange peel waste and olive pulp could be anaerobically digested to produce high methane yields. Wheat straw was not digestible. In a packed bed reactor, anaerobic digestion was not initiated above bulk densities of 100 kg/m³ for peel waste and 75 kg/m³ for olive pulp. Interestingly, after the digestion has been initiated and balanced methanogenesis established, the decomposing biomass could be packed to higher densities and successfully digested. These observations provided useful insights for high throughput reactor designs. Another outcome from this project was the development of low cost devices to measure methane content of biogas for off-line (US$37), field (US$50), and online (US$107) applications.