THE DECADENCE OF THE BET-ʾASGÄDÄ ARISTOCRATIC SYSTEM AND THE EMANCIPATION OF THE TǝGRÄ (1890-1948)

Per secoli gli altopiani settentrionali dell'Eritrea hanno ospitato gruppi di immigrati di diversa origine. Nel sedicesimo secolo ci fu il reinsediamento della famiglia di Bʾǝmnät (ብእምነት), in seguito noto come Bet-ʾAsgädä (ቤት ኣስገደ) dopo una delle migrazioni di suo figlio a Sahǝl (ሳሕል). Partirono da ʿAdi-Nǝfas (ዓዲ ንፋስ), di Ḥamasen (ሓማሴን) insieme a numerose famiglie e persone di varie professioni e si stabilirono negli altopiani del Sahǝl. A causa della geografia e del clima, i vari antichi abitanti dell'area del Sahǝl conducevano una vita pastorale. Si spostavano stagionalmente dagli altopiani alle pianure costiere a est, e dalle pianure occidentali fino all’attuale Sudan. La piccole dimensioni e la natura mobile dell'organizzazione sociale nomade avevano reso i clan vittime di qualsiasi forza bellica organizzata. La lotta per il potere della famiglia Bʾǝmnät e l'economia sedentaria in patria diedero loro una relativa superiorità guerriera e organizzativa sui clan ospitanti Tǝgrä (ትግረ). In nessun momento i Bet-ʾAsgädä si sono imposti come signori della terra e del popolo nella regione, con la responsabilità di difendere eventuali incursioni e diritti di pascolo, in cambio i sudditi offrivano gabelle e servizi. Tale fornitura di imposte e di servizi fece sì che i signori noti anche come i Šumaglä (ሹማግለ) abbandonassero la loro tradizione agricola e dipendessero interamente dai doni Tǝgrä. La consolidata aristocrazia Tǝgrä-Šumaglä dei Bet-ʾAsgädä continuò con un'economia nomade predominante. Tale classificazione e relazione binaria tra proprietari terrieri e pastori fu quasi un'esperienza unica nel suo genere rispetto alle pratiche feudali convenzionali fino a quando non crollò definitivamente alla fine degli anni '40. Pertanto, questa dissertazione cerca di scoprire l'indebolimento e il declino del rapporto aristocratico. Di fronte al diverso dinamismo politico della regione, l'ordine aristocratico ha resistito fino al XX secolo. Numerose forze politiche e movimenti religiosi si aggirarono e si stabilirono nella regione di Bet-ʾAsgädä, numerosi imperi regionali e viceré assoggettarono la regione ma senza alcun cambiamento fondamentale nella natura del legame aristocratico. Quindi, questa tesi si sforza di investigare sul perché la fine dell’aristocrazia, che ha preannunciato l'emancipazione del Tǝgrä è avvenuta nel periodo britannico piuttosto che prima o dopo? Infine, i risultati della tesi sostengono che, analogamente alla natura debole e 2 Sahǝl (ሳሕል) è la parte settentrionale dell'Eritrea. Confina con il Sudan e il Mar Rosso, rispettivamente a nord-ovest e ad est. Gli altopiani settentrionali o it territorio di Bet-ʾAsgädä in esame si trovano all’interno di questa regione. Disorganizzata dei Tǝgrä che mettevano in soggezione, la loro emanicipazione fu raggiunta grazie agli elementi che causarono l’inevitabile decadenza del Sistema aristocratico. Questi includevano; l'intervento capitalista formale e informale del sistema coloniale italiano, la forte resistenza e unità del Tǝgrä sotto la guida di individui coscienti e istruiti e la buona volontà dell'amministrazione britannica. Come indagine storica, questo lavoro seguirà gli sviluppi cronologici per dimostrare una relativa veridicità di spiegazione e ricostruzione del processo del declino dell'aristocrazia Bet-ʾAsgädä e della successiva emancipazione delle comunità Tǝgrä

Diabetes Mellitus and Obesity as Risk Factors for Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest types of cancer. The worldwide estimates of its incidence and mortality in the general population are eight cases per 100,000 person-years and seven deaths per 100,000 person-years, and they are significantly higher in the United States than in the rest of the world. The incidence of this disease in the United States is more than 50,000 new cases in 2017. Indeed, total deaths due to PDAC are projected to increase dramatically to become the second leading cause of cancer-related deaths before 2030. Considering the failure to date to efficiently treat existing PDAC, increased effort should be undertaken to prevent this disease. A better understanding of the risk factors leading to PDAC development is of utmost importance to identify and formulate preventive strategies. Large epidemiologic and cohort studies have identified risk factors for the development of PDAC, including obesity and type 2 diabetes mellitus. This review highlights the current knowledge of obesity and type 2 diabetes as risk factors for PDAC development and progression, their interplay and underlying mechanisms, and the relation to diet. Research gaps and opportunities to address this deadly disease are also outlined

Alternative p38MAPKs as biomarkers in the interplay of colon cancer and inflammatory bowel diseases

Trabajo presentado en el 44º Congreso Nacional de la Sociedad Española de Bioquímica y Biología Molecular (SEBBM), celebrado en Málaga (España) del 06 al 09 de septiembre de 2022.Chronic inflammation in inflammatory bowel disease (IBD) is a risk factor for Colorectal cancer (CRC) development, but our understanding of this interplay at a molecular level is still limited. p38γ and p38δ, are central in the development of mouse colitis-associated CRC (CAC) by modulating the inflammatory immune response. However, their implication in human CRC and IBD is not well defined. In this study we perform an integrative analysis of p38γ and p38δ mRNA and protein expression and activation in human patients; using human CRC derived organoids and plasma samples, as well as data from different human CRC and IBD mRNA databases. We found that, p38δ levels were decreased, whereas p38γ expression and phosphorylation were significantly increased in CRC compared to normal colon samples. This increase correlated with the expression of genes implicated in inflammation. Examine of p38γ/p38δ in IBD patients showed that p38γ mRNA and protein levels were increased in Crohn’s disease and ulcerative colitis patients. Contrary, p38δ mRNA was significantly decreased. We also investigated the expression of miRNAs, miR-128-2, miR133a and miR-155, implicated in inflammation and cancer development. In mouse model of colitis and CAC, miR128-2 level was regulated by p38γ/p38δ. In the plasma of IBD and CRC patients, miR128-2 was increased compared to healthy donors, and this correlated with p38γ and p38δ levels. Our results show an opposite regulation of p38γ and p38δ in both CRC and IBD; and suggest that p38γ acts as a link between colitis and CRC by favouring an inflammatory environment that promotes tumour development. We provided evidence that p38γ/p38δ, together with miR-128-2, can be useful as biomarkers, and as potential treatment targets, for colitis and early-stage CRC

p38γ and p38δ as biomarkers in the interplay of colon cancer and inflammatory bowel diseases

descripción no proporcionada por scopusThis research was funded by the MCIN/AEI/10.13039/501100011033 (PID2019-108349RB100 and SAF2016-79792R) to AC and JJSE; Villum Foundation, grant no. 13152 to KA; by Agencia Estatal de Investigación (PID2019-104867RBI00/AEI/10.13039/501100011033) and the Instituto de Salud Carlos III- Fondo Europeo de Desarrollo Regional (CIBERONC/CB16/12/00273 and ICI20/00057) to AM and AB. PF received MCIN FPI fellowship (BES-2017-080139)

Evaluation of a Mixed Meal Test for Diagnosis and Characterization of PancrEaTogEniC DiabeTes Secondary to Pancreatic Cancer and Chronic Pancreatitis: Rationale and Methodology for the DETECT Study From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer

Pancreatogenic diabetes mellitus is most commonly the result of chronic pancreatitis but can also occur secondary to pancreatic cancer. The early identification of pancreatogenic diabetes and distinction from the more prevalent type 2 diabetes are clinically significant; however, currently, there is no validated method to differentiate these diabetes subtypes. We describe a study, "Evaluation of a Mixed Meal Test for Diagnosis and Characterization of PancrEaTogEniC DiabeTes Secondary to Pancreatic Cancer and Chronic Pancreatitis: the DETECT study," that seeks to address this knowledge gap. The DETECT study is a multicenter study that will examine differences in hormone and glucose excursions after a mixed meal test. The study will also create a biorepository that will be used to evaluate novel diagnostic biomarkers for differentiating these diabetes subtypes

Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer

Diabetes mellitus is a group of diseases defined by persistent hyperglycaemia. Type 2 diabetes, the most prevalent form, is characterised initially by impaired insulin sensitivity and subsequently by an inadequate compensatory insulin response. Diabetes can also develop as a direct consequence of other diseases, including diseases of the exocrine pancreas. Historically, diabetes due to diseases of the exocrine pancreas was described as pancreatogenic or pancreatogenous diabetes mellitus, but recent literature refers to it as type 3c diabetes. It is important to note that type 3c diabetes is not a single entity; it occurs because of a variety of exocrine pancreatic diseases with varying mechanisms of hyperglycaemia. The most commonly identified causes of type 3c diabetes are chronic pancreatitis, pancreatic ductal adenocarcinoma, haemochromatosis, cystic fibrosis, and previous pancreatic surgery. In this Review, we discuss the epidemiology, pathogenesis, and clinical relevance of type 3c diabetes secondary to chronic pancreatitis and pancreatic ductal adenocarcinoma, and highlight several important knowledge gaps

Keratin 8 expression in colon cancer associates with low faecal butyrate levels

<p>Abstract</p> <p>Background</p> <p>Butyrate has been implicated in the mechanistic basis of the prevention of colorectal cancer by dietary fibre. Numerous in vitro studies have shown that butyrate regulates cell cycle and cell death. More recently we have shown that butyrate also regulates the integrity of the intermediate filament (IF) cytoskeleton <it>in vitro</it>. These and other data suggest a link between the role of diet and the implication of a central role for the keratin 8 (K8) as guardian of the colorectal epithelium.</p> <p>Methods</p> <p>In this cross-sectional study possible links between butyrate levels, field effects and keratin expression in cancer were addressed directly by analysing how levels of expression of the IF protein K8 in tumours, in adjacent fields and at a distant landmark site may be affected by the level of butyrate in the colon microenvironment. An immunohistochemical scoring protocol for K8 was developed and applied to samples, findings were further tested by immunoblotting.</p> <p>Results</p> <p>Levels of K8 in colorectal tumours are lower in subjects with higher levels of faecal butyrate. Immunoblotting supported this finding.Although there were no significant relationships with butyrate on the non-tumour tissues, there was a consistent trend in all measures of extent or intensity of staining towards a reduction in expression with elevated butyrate, consistent with the inverse association in tumours.</p> <p>Conclusions</p> <p>The data suggest that butyrate may associate with down-regulation of the expression of K8 in the cancerized colon. If further validated these findings may suggest the chemopreventive value of butyrate is limited to early stage carcinogenesis as low K8 expression is associated with a poor prognosis.</p

A Mucosal and Cutaneous Chemokine Ligand for the Lymphocyte Chemoattractant Receptor GPR15

Chemoattractants control lymphocyte recruitment from the blood, contributing to the systemic organization of the immune system. The G protein-linked receptor GPR15 mediates lymphocyte homing to the large intestines and skin. Here we show that the 9 kDa CC-motif containing cationic polypeptide AP57/colon-derived sushi containing domain-2 binding factor (CSBF), encoded by C10orf99 in the human and 2610528A11Rik in the mouse, functions as a chemokine ligand for GPR15 (GPR15L). GPR15L binds GPR15 and attracts GPR15-expressing T cells including lymphocytes in colon-draining lymph nodes and Vγ3+ thymic precursors of dermal epithelial T cells. Patterns of GPR15L expression by epithelial cells in adult mice and humans suggest a homeostatic role for the chemokine in lymphocyte localization to the large intestines, as well as a role in homing to the epidermis during wound healing or inflammation. GPR15L is also significantly expressed in squamous mucosa of the oral cavity and esophagus with still poorly defined regulation. Identification of the chemotactic activity of GPR15L adds to its reported antibacterial and tumor cell growth regulatory functions and suggests the potential of targeting GPR15L–GPR15 interactions for modulation of mucosal and cutaneous inflammation

An Antibiotic-Responsive Mouse Model of Fulminant Ulcerative Colitis

Paul Allen and colleagues describe the development of a mouse model of fulminant ulcerative colitis with multiple genetic hits in immune regulation which can be moderated by anti-cytokine therapy and broad-spectrum antibiotics