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2022 ◽  
Vol 12 (2) ◽  
pp. 386-392
Author(s):  
Bo Qian ◽  
Hongmei Zhang ◽  
Jijun Zhang ◽  
Chao Bai ◽  
Wencai Sun

Mesenchymal stem cells (MSCs) are indicated to severe pancreatitis (SAP), whilst level of Shh/GLi axis varies in severe acute pancreatitis (SAP). However, little is known the interaction between MSCs and Shh in SAP. In this study, we established animal model of SAP in 10 rats and transplanted MSCs into 10 rats, with another 10 sham-operated rats as control group. The pathological changes of rat pancreatic tissue were observed. ELISA was conducted to determine the MPO level of pancreatic inflammation, and Western blot to detect the expression level of Shh, Gli1 and Gli2 in tissues. Administration of MSCs remarkably alleviated the pancreatic tissue necrosis and inflammation and decreased blood loss in SAP rats. Up-regulated expression of Shh, Gli1 and Gli2 was observed in SAP tissues when compared to tissues in control group, but their expressions declined in the presence of MSCs, and 24 hour later returned to normal levels. Collectively, MSCs regulates the balance of Shh/GLi axis by decreasing Shh and Gli1, thereby attenuating progression and symptoms of SAP.


Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 128
Author(s):  
Andrew Gdowski ◽  
Hamed Hayatshahi ◽  
Rafal Fudala ◽  
Rohan Joshi ◽  
Jin Liu ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and is the fourth leading cause of cancer-related deaths in the United States. Unfortunately, 80–85% of patients are diagnosed with unresectable, advanced stage tumors. These tumors are incurable and result in a median survival less than approximately six months and an overall 5-year survival rate of less than 7%. Whilst chemotherapy is a critical treatment, cure is not possible without surgical resection. The poor clinical outcomes in PDAC can be partially attributed to its dense desmoplastic stroma, taking up roughly 80% of the tumor mass. The stroma surrounding the tumor disrupts the normal architecture of pancreatic tissue leading to poor vascularization, high intratumoral pressure along with hypoxia and an acidic tumor microenvironment. This complicated microenvironment presents a significant challenge for drug delivery. The current manuscript discusses a novel approach to overcome many of these various obstacles. A complex of gemcitabine (GEM) and hemoglobin S (HbS) was formulated, which self-polymerizes under hypoxic and acidic conditions. When polymerized, HbS has the potential to break the tumor stroma, decrease intratumoral pressure, and therefore improve the treatment efficacy of standard therapy. Intratumoral injection of HbS with a fluorescent small molecule surrogate for GEM into a pancreatic tumor xenograft resulted in improved dissemination of the small molecule throughout the pancreatic tumor. The self-polymerization of HbS + GEM was significantly more effective than either agent individually at decreasing tumor size in an in vivo PDAC mouse model. These findings would suggest a clinical benefit from delivering the complex of GEM and HbS via direct injection by endoscopic ultrasound (EUS). With such a treatment option, patients with locally advanced disease would have the potential to become surgical candidates, offering them a chance for cure.


Folia Medica ◽  
2021 ◽  
Vol 63 (6) ◽  
pp. 875-883
Author(s):  
Agung Putra ◽  
Zakariya Hadi Suwiryo ◽  
Adi Muradi Muhar ◽  
Agus Widyatmoko ◽  
Fifin Luthfia Rahmi

Introduction: Diabetes is a heterogeneous group of metabolic diseases characterized by elevated blood glucose due to autoimmune disorder or a combination of insulin resistance and insulin deficiency. VEGF and PDGF are the main actors in the regeneration of damaged pancreatic tissue. However, the prolonged release of these molecules may induce fibrosis formation. Mesenchymal stem cells (MSCs) have a high potential to regenerate damaged pancreatic tissue by releasing PDGF and VEGF. Aim: This study aimed to investigate the effect of MSCs on the levels of PDGF and VEGF on days 2 and 44 in diabetic mice and determine the number of pancreatic islet cells and blood glucose levels. Materials and methods: This study used a post-control group design with animals divided into five groups: sham, control, and three treatment groups (P) which were given MSCs at doses of 1.5×105, 3×105, and 6×105 cells. The levels of PDGF, VEGF, and blood glucose were measured by enzyme-linked immunosorbent assay (ELISA), while the number of pancreatic islet cells was analyzed using H&E staining. Results: This study showed a significant increase of VEGF and PDGF levels on day 2 and a significant increase in islet cell percentages on day 44 in line with the decreased blood glucose level. However, there was no difference between VEGF and PDGF levels on day 44. Conclusions: MSCs regulate PDGF and VEGF levels in wound healing phases and remodel pancreatic islet β-cells regeneration to control blood glucose in diabetic model mice.


Author(s):  
R.M. Uruzbaev ◽  
E.D. Khadieva ◽  
N.V. Zharkov ◽  
Yu.Yu. Kopylova ◽  
L.V. Vikhareva ◽  
...  

Superinvasive opisthorchiasis involves many body systems in the pathological process. The parasite, due to its unique characteristics, changes numerous genes, and contributes to proliferative processes. Stem cells are initiated and subsequently differentiated along various cell lineages. The liver and pancreas are econiches, where parasites vegetate for a long time. However, there is no available information on the dynamics of proliferative pancreatic changes and various histogenetic pathways. The aim of the paper is to reveal the proliferative activity of pancreatic stem cells in superinvasive opisthorchiasis and their differentiation. Materials and Methods. Fragments of pancreatic tissue were selected and analyzed in departments of morbid anatomy of medical institutions located on the territory of the hyperendemic focus (Tyumen region, Omsk region, Khanty-Mansiysk Autonomous Okrug). The following groups were formed: Group 1 – patients with a history of superinvasive opisthorchiasis with a more than 10-year invasion (n=70); Group 2 – patients without invasion with all-cause mortality (n=10). The material was subjected to routine histological examination. The authors used histochemical and immunohistochemical staining methods and performed statistical analysis. Results. The authors observed marked proliferative reactions in the epithelial layer of the duct system, the secretory section of the pancreas, as well as changes in the endocrine apparatus. The histological types of pancreatic endocrine formations were revealed, namely, normal, hyperplastic and newly formed islets of Langerhans. The difference between the newly formed islets and the preexisting forms was in a disorderly arrangement, an indefinite shape, significantly larger sizes, and in the absence or presence of a forming capsule. The newly formed islets contained cells similar to preexisting endocrinocytes. Conclusion. Under the influence of the Opisthorchis felineus secretome, there occurs initiation and differentiation of pancreatic stem cells. Newly formed clusters of endocrine cells are formed, but they have the characteristics of the preexisting endocrine apparatus and secretory cells with exocrine properties. Key words: pancreas, opisthorchiasis, secretion, superinvasion, stem cells, differentiation. Суперинвазионный описторхоз – заболевание, при котором в патологический процесс вовлекаются многие системы организма. Паразит вследствие своих уникальных свойств изменяет многочисленные гены, дает начало пролиферативным процессам. Происходит инициация стволовых клеток с последующей дифференцировкой их по линиям различных дифферонов. Печень и поджелудочная железа являются эконишами, где длительное время вегетируют паразиты, однако сведений о динамике пролиферативных изменений в железе с рассмотрением различных гистогенетических путей в литературе не представлено. Цель работы. Выявить пролиферативную активность стволовых клеток поджелудочной железы при суперинвазионном описторхозе и их дифференцировку. Материалы и методы. Фрагменты ткани поджелудочной железы были отобраны для изучения в патологоанатомических отделениях медицинских учреждений, расположенных на территории гиперэндемического очага (Тюменская, Омская области, Ханты-Мансийский автономный округ). Сформированы следующие группы: 1 группа – лица, в анамнезе которых имелся суперинвазионный описторхоз с длительностью инвазии более 10 лет (n=70); 2 группа – лица без инвазии, умершие от случайных причин (n=10). Материал подвергался рутинному гистологическому исследованию, использовались гистохимические и иммуногистохимические методы окрашивания, проводился статистический анализ. Результаты. Обнаружены выраженные пролиферативные реакции в эпителиальном пласте протоковой системы, секреторном отделе поджелудочной железы и изменения структуры эндокринного аппарата. Выявлены гистологические типы эндокринных образований поджелудочной железы: островки Лангерганса обычного строения, гиперплазированные и новообразованные островки. Отличие последних от предсуществующих форм состояло в беспорядочном расположении, неопределенной форме, существенно более крупных размерах, отсутствии или наличии формирующейся капсулы. Новообразованные островки содержали аналогичные клетки, обладающие идентичными свойствами предсуществующих эндокриноцитов. Выводы. При воздействии секретома Opisthorchis felineus происходит инициация и дифференцировка стволовых клеток поджелудочной железы с формированием новообразованных скоплений эндокринных клеток со свойствами предсуществующего эндокринного аппарата и секреторных клеток с экзокринными свойствами. Ключевые слова: поджелудочная железа, описторхоз, секретом, суперинвазия, стволовые клетки, дифференцировка.


2021 ◽  
Author(s):  
Kenneth N Aycock ◽  
Sabrina N. Campelo ◽  
Rafael V. Davalos

Abstract Irreversible electroporation (IRE), otherwise known as non-thermal pulsed field ablation (PFA), is an attractive focal ablation modality due to its ability to destroy aberrant cells with limited disruption of extracellular tissue architecture. Despite its non-thermal cell death mechanism, application of electrical energy results in Joule heating that, if ignored, can cause undesired thermal injury. Engineered thermal mitigation (TM) technologies including phase change materials (PCMs) and active cooling (AC) have been reported and tested in isolated preliminary studies to limit the risk of thermal damage, but their performance compared to one another is relatively unknown. Further, the effects of pulsing paradigm, electrode geometry, PCM composition, and chosen active cooling parameters have not been examined. Here, we develop a computational model of conventional bipolar and monopolar probes with solid, PCM-filled, or actively cooled cores and simulate clinical IRE treatments in pancreatic tissue. We find that probes with integrated PCM cores can be tuned to drastically limit thermal damage compared to traditional solid probes. Actively cooled probes, on the other hand, provide even more control over thermal effects within the probe vicinity and can altogether eliminate thermal damage. In practice, these differences in performance are tempered by the increased time, expense, and effort necessary to use actively cooled probes compared to traditional solid probes or those containing a PCM core.


2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
Franko Shing Fun Ngan ◽  
Srishti Sarkar ◽  
Ali Arshad ◽  
Ben Maher ◽  
Nadeem Tehami ◽  
...  

Abstract Background The use of EUS (endoscopic ultrasound) guided drainage with endoscopic LAMS (lumen apposing metal stent) necrosectomy is an emerging treatment option for walled-off pancreatic necrosis (WOPN) secondary to acute severe pancreatitis. It can delay or remove the need for surgical necrosectomy, which can be associated with high morbidity and mortality. However, the endoscopic approach is not always successful due to a multitude of factors and salvage transgastric necrosectomy can be performed using the tract created by the LAMS to achieve internal drainage and remove necrotic pancreas.  Methods We describe our unit’s experience in managing WOPN in two patients. We suggest a treatment pathway of WOPN which includes a step-up approach including salvage transgastric necrosectomy in patients where multiple endoscopic necrosectomies and washouts have failed.  Results Two patients, aged 67 and 69, were admitted as intensive care transfers for gallstone and alcohol pancreatitis respectively. They underwent a step-up approach to treat their infected WOPN, starting with the deployment of LAMS and endoscopic necrosectomy. They both showed brief clinical improvement after repeated endoscopic necrosectomy but further imaging showed ongoing large collections that could not be treated endoscopically. Both patients underwent successful transgastric open necrosectomy where necrotic pancreatic tissue was accessed surgically through the already created cyst-gastrostomy. This had the advantage of internal drainage of the collection into the stomach without the need for external surgical drains. Conclusions The emphasis in the treatment of WOPN has shifted to minimally invasive percutaneous or endoscopic drainage modalities. Endoscopically inserted LAMS may not always achieve definitive drainage of the WOPN but should be employed in the first instance as they are associated with reduced morbidity and mortality compared to surgery. Ultimately, open necrosectomy with washout remains the definitive management strategy in the step-up approach. We believe that the trans-gastric open necrosectomy approach can be used successfully in patients where the minimally invasive approach has failed. 


2021 ◽  
Vol 3 (2) ◽  
pp. 57
Author(s):  
Mutiarani Dasha Hanggaresty ◽  
Ni Kadek Warditiani

Background: Diabetes mellitus which is characterized by hyperglycemia is a metabolic disease due to insulin action, defects in insulin secretion, or both. Various studies have shown that herbs that have a hypoglycemic effect can be used in the treatment of diabetes mellitus. Generally, herbs can slow down the complications of diabetes mellitus and improve metabolism. The ability of plants to restore the function of pancreatic tissue to increase insulin production or make it easier for insulin to process glucose is related to the effects of hypoglycemia. Objective: Comparing plants that have a hypoglycemic activity that can be used in the treatment of diabetes mellitus in Indonesia. Methods: studying literature from various databases, websites, national journals, and relevant international journals to identify plants that have hypoglycemic activity. Results: The mechanism A. sativum as a hypoglycemic involves different fiber viscosities; A. vera involved as a hypoglycemic by protecting pancreatic? cells; Asiatic acid in C. asiatica increasing glycolysis by restoring the activity of key enzymes; G. max inhibiting ?-amylase and the stigmasterol increasing the absorption of blood glucose and reducing insulin resistance; P. macrocarpa exert their antidiabetic action via ?-glucosidase modulation, an extra distinctive pancreatic mechanism; S. arvensis has the potential to inhibit ?-amylase enzymes. Conclusions: This review article has presented 6 detailed comparisons of plants that have a hypoglycemic activity that can be used in the treatment of diabetes mellitus in Indonesia and we believe can be useful for students, researchers, or practitioners. Keywords: Diabetes mellitus, hypoglycemia, Indonesian plants


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Hongmin Xu ◽  
Lei Zhang ◽  
Hua Kang ◽  
Jie Liu ◽  
Jiandong Zhang ◽  
...  

Background and Purpose. Carbohydrate antigen 19-9 (CA19-9) based approaches differentiate less than 60% of cases of pancreatic cancer (PC) from those of pancreatic tissue damage caused by chronic pancreatitis and type 2 diabetes mellitus (DM). This study aims to identify potential blood-derived candidate biomarkers for improved diagnosis sensitivity. Methods. Plasma metabolic profiles in 26 PC patients, 27 DM patients, and 23 healthy volunteers were examined using an ultraperformance liquid chromatography coupled with tandem mass spectrometry platform. Differential metabolite ions were then identified using the principal component analysis (PCA) model and the orthogonal partial least-squares discrimination analysis (OPLS-DA) model. The diagnosis performance of metabolite biomarkers was validated by logistic regression models. Results. We established a PCA model (R2X = 23.5%, Q2 = 8.21%) and an OPLS-DA model (R2X = 70.0%, R2Y = 84.9%, Q2 = 69.7%). LysoPC (16 : 0), catelaidic acid, cerebronic acid, nonadecanetriol, and asparaginyl-histidine were found to identify PC, with a sensitivity of 89% and a specificity of 91%. Besides, lysoPC (16 : 0), lysoPC (16 : 1), lysoPC (22 : 6), and lysoPC (20 : 3) were found to differentiate PC from DM, with higher accuracy (68% versus 55%) and higher AUC values (72% versus 63%) than those of CA19-9. The diagnostic performance of metabolite biomarkers was finally validated by logistic regression models. Conclusion. We succeeded in screening differential metabolite ions among PC and DM patients and healthy individuals, thus providing a preliminary basis for screening the biomarkers for the early diagnosis of PC.


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