Intracellular Ca2+ Signalling in the Pathogenesis of Acute Pancreatitis: Recent Advances and Translational Perspectives

Intracellular Ca2+ signalling is a major signal transductional pathway in non-excitable cells, responsible for the regulation of a variety of physiological functions. In the secretory epithelial cells of the exocrine pancreas, such as acinar and ductal cells, intracellular Ca2+ elevation regulates digestive enzyme secretion in acini or fluid and ion secretion in ductal cells. Although Ca2+ is a uniquely versatile orchestrator of epithelial physiology, unregulated global elevation of the intracellular Ca2+ concentration is an early trigger for the development of acute pancreatitis (AP). Regardless of the aetiology, different forms of AP all exhibit sustained intracellular Ca2+ elevation as a common hallmark. The release of endoplasmic reticulum (ER) Ca2+ stores by toxins (such as bile acids or fatty acid ethyl esters (FAEEs)) or increased intrapancreatic pressure activates the influx of extracellular Ca2+ via the Orai1 Ca2+ channel, a process known as store-operated Ca2+ entry (SOCE). Intracellular Ca2+ overload can lead to premature activation of trypsinogen in pancreatic acinar cells and impaired fluid and HCO3- secretion in ductal cells. Increased and unbalanced reactive oxygen species (ROS) production caused by sustained Ca2+ elevation further contributes to cell dysfunction, leading to mitochondrial damage and cell death. Translational studies of AP identified several potential target molecules that can be modified to prevent intracellular Ca2+ overload. One of the most promising drugs, a selective inhibitor of the Orai1 channel that has been shown to inhibit extracellular Ca2+ influx and protect cells from injury, is currently being tested in clinical trials. In this review, we will summarise the recent advances in the field, with a special focus on the translational aspects of the basic findings

Cystic Fibrosis of the Pancreas: The Role of CFTR Channel in the Regulation of Intracellular Ca2+ Signaling and Mitochondrial Function in the Exocrine Pancreas

Cystic fibrosis (CF) is the most common genetic disorder that causes a significant damage in secretory epithelial cells due to the defective ion flux across the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. Pancreas is one of the organs most frequently damaged by the disease leading to pancreatic insufficiency, abdominal pain and an increased risk of acute pancreatitis in CF patients causing a significant decrease in the quality of life. CFTR plays a central role in the pancreatic ductal secretory functions by carrying Cl- and HCO3- ions across the apical membrane. Therefore pathophysiological studies in CF mostly focused on the effects of impaired ion secretion by pancreatic ductal epithelial cells leading to exocrine pancreatic damage. However, several studies indicated that CFTR has a central role in the regulation of intracellular signaling processes and is now more widely considered as a signaling hub in epithelial cells. In contrast, elevated intracellular Ca2+ level was observed in the lack of functional CFTR in different cell types including airway epithelial cells. In addition, impaired CFTR expression has been correlated with damaged mitochondrial function in epithelial cells. These alterations of intracellular signaling in CF are not well characterized in the exocrine pancreas yet. Therefore in this review we would like to summarize the complex role of CFTR in the exocrine pancreas with a special focus on the intracellular signaling and mitochondrial function

Pszichoszociális változás és az átalakulás retorikája a tizenkét lépéses mozgalmakban = Psychosocial change and the rhetoric of transformation in Twelve Steps movements

Kutatásunkban felépülő szenvedélybetegek interjúszövegeit vizsgáltuk, komplex tartalomelemző eljárásokkal. Két eltérő felépülési modellt vázoltunk fel: az egyik a domináns kultúrával több izomorfiát mutató Alkoholizmus Ellenes Klubok, a másik pedig a 12-lépéses közösségek alternatív, komplementer jellegű gyakorlata. A 12-lépéses közösségeknél hangsúlyosabb a tanulási folyamat, a személyesen megélt igazság keresése, a kontroll rendszerszintű értelmezése. A markáns dialogikus jelleg és a szelf-reflektivitás arra utal, hogy a tagok az autobiografikus hozzáállás kialakításával, a mentalizációs képesség fejlesztésével segítik a felépülést. Az Alkoholizmus Ellenes Klubok tagjainál gyakoribb a versengés, az „abszolút” típusú kognitív szűrők, az általánosítások, a konverzációs sablonok. Fontosak a kauzális magyarázatok, mint a koherencia megteremtésének legfőbb eszközei, jellemző a spiritualitás konform értelmezése, gyakoribbak a felépülő családjára tett utalások. A felépülés közös tényezői: a sorstársi közösség (közös tapasztalatok, egymás szolgálata); a tág értelemben vett spiritualitás; a törekvés, hogy értelmezzék saját tapasztalataikat, és újrarendezzék saját történeteiket. Újabban a forrás-szűkítések hatására a deficit modellek helyett az erőforrás-alapú felépülési modellek előtérbe kerülnek. Kutatásunk - az egészségtanulás jegyében – előkészítése a generativitás, az intergenerációs transzmisszió megváltoztatása és a poszt-traumás növekedés további kutatási programjainak. | In the current study interviews with recovering addicts were analyzed with complex methods. Two different recovery models were identified: one reflecting the conventions of Anti- Alcoholism Club members, isomorphic with the dominant culture; and the alternative, complementary culture of 12-step fellowships. 12-step communities highlight the learning process during recovery, search for some personal truth, and systemic forms of control. The dialogic nature of the texts, together with self-reflectivity, indicates that members facilitate their recovery by establishing an autobiographic stance and developing mentalization capacity. With AAC members, a competitive approach could be identified. Cognitive filters, generalizations and conventional phrases were characteristic of the texts. Linear causal explanations served as means to establish coherence. Spirituality was understood in a more conservative manner. References to the recovering addict’s family were significantly more frequent. Common factors of recovery: fellows’ community (similar experiences, serving one another); spirituality (in any sense); striving for making meaning of own experiences, and restructure personal stories accordingly. Recently, strength-based recovery models as cost-effective therapeutic solutions have been emphasized. Our research may serve as a basis for further studies in health learning concerning generativity, changing intergenerational transmission models and post-traumatic growth

Reduction of intracellular oxidative stress with copper incorporated layered double hydroxide

Biocompatible Cu(II)-doped layered double hydroxide (CMA) nanoparticles were developed to combat reactive oxygen species. The 2-dimensional nanozymes showed both superoxide dismutase and catalase-like activity in chemical assays, while proved as..