BACKGROUND Acinar cystic transformation(ACT)of the pancreas is a rare non-neoplastic transformation of the pancreas.Adult women are the majority of patients with ACT,but few cases have been reported in pediatric patie...BACKGROUND Acinar cystic transformation(ACT)of the pancreas is a rare non-neoplastic transformation of the pancreas.Adult women are the majority of patients with ACT,but few cases have been reported in pediatric patients.Given that there are currently no guidelines for the treatment of ACT,current treatment is based primarily on expert opinions and clinical experiences.Here,we report the case of the youngest child with ACT to date.Additionally,a literature review on pediatric ACT cases was performed to summarize previous clinical experience and treatment methods.CASE SUMMARY A 1-year-old Chinese girl presented with progressive abdominal distension for 6 months.A detailed consultation revealed an uneventful history.The patient showed no signs of fever or abdominal pain and had a good appetite and normal feces.A mass of about 20 cm×10 cm×10 cm in size was detected in the abdomen.Both abdominal ultrasound and computed tomography examination revealed a multilocular cystic mass about 21.7 cm×16.8 cm×8.9 cm in size.At first,due to the large size and the possible retroperitoneal origin of the cyst,a total resection of the lesion was not possible.A single-port laparoscopic lymphangioma puncture and Pingyangmycin injection were performed in March 2023.One month after surgery,the abdominal cyst rapidly enlarged to its pre-operative size.After consulting with the experts in the angiology department and interventional department,sclerotherapy combined with oral sirolimus was performed in May 2023.After confirming that the tumor was not sensitive to sclerotherapy combined with oral sirolimus,our surgical team performed tumor reduction in August 2023.This surgery confirmed that the polycystic mass originated from the head of the pancreas,and pathological and immunohistochemical findings diagnosed pancreatic ACT.The patient showed no signs of cyst lesions after 6 months of follow-up and remains in good health up to the time of this report.CONCLUSION ACT is a rare non-neoplastic transformation of the pancreas,more rarely seen in children.Manifestation and examinations show no specificity for diagnosis,and final diagnosis is mainly based on histological findings.To reach a specific diagnosis and rule out malignancy is a priority in clinical practice,and repeated biopsy or radical surgery should be considered before malignancy is ruled out.However,once a diagnosis of ACT is made,a conser-vative treatment with consecutive follow-up is recommended until symptoms present or obvious enlargement occurs because ACT is considered a slow-growing and benign tumor.展开更多
To the Editor:Pancreatic acinar cell carcinoma(PACC),with primary compo-nent similar to acinar cells,represents merely 1%-2%of pancreatic exocrine neoplasms[1].As a high-grade malignancy,PACC has the potential to mani...To the Editor:Pancreatic acinar cell carcinoma(PACC),with primary compo-nent similar to acinar cells,represents merely 1%-2%of pancreatic exocrine neoplasms[1].As a high-grade malignancy,PACC has the potential to manifest in any anatomical region of the pancreas,while mostly in the head of the pancreas[2].The initial symptoms of PACC may not be obvious.Upon diagnosis,the tumor typi-cally manifests as a substantial size,resulting in compression of adjacent organs and subsequent non-specific gastrointestinal mani-festations.These complications encompass abdominal pain,nausea,diarrhea,and weight loss[3].Nevertheless,the incidence of bile duct obstruction and jaundice is relatively modest.Despite being classified as an aggressive tumor,PACC exhibits a slightly slower disease progression compared to pancreatic ductal adenocarcinoma(PDAC).Currently,the median survival of PACC ranges from 18 to 47 months[4].Here,we presented a unique occurrence of PACC with liver metastases,aiming to enhance comprehension of the disease and diminish the probability of misdiagnosis.展开更多
Xerostomia(dry mouth)is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren’s syndrome,with no permanent cure existing for this debilitating condition.To this e...Xerostomia(dry mouth)is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren’s syndrome,with no permanent cure existing for this debilitating condition.To this end,in vitro platforms are needed to test therapies directed at salivary(fluid-secreting)cells.However,since these are highly differentiated secretory cells,the maintenance of their differentiated state while expanding in numbers is challenging.In this study,the efficiency of three reversible thermo-ionically crosslinked gels:(1)alginate–gelatin(AG),(2)collagen-containing AG(AGC),and(3)hyaluronic acid-containing AG(AGHA),to recapitulate a native-like environment for human salivary gland(SG)cell expansion and 3D spheroid formation was compared.Although all gels were of mechanical properties comparable to human SG tissue(~11 kPa)and promoted the formation of 3D spheroids,AGHA gels produced larger(>100 cells/spheroid),viable(>93%),proliferative,and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins(aquaporin-5,NKCC1,ZO-1,α-amylase)for 14 days in culture.Moreover,the spheroids responded to agonist-induced stimulation by increasingα-amylase secretory granules.Here,we propose alternative lowcost,reproducible,and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact,highly viable 3D-SG spheroids.展开更多
Pancreatic ductal adenocarcinoma(PDAC) is a common pancreatic cancer and the fourth leading cause of cancer death in the United States. Treating this life-threatening disease remains challenging due to the lack of eff...Pancreatic ductal adenocarcinoma(PDAC) is a common pancreatic cancer and the fourth leading cause of cancer death in the United States. Treating this life-threatening disease remains challenging due to the lack of effective prognosis, diagnosis and therapy. Apart from pancreatic duct cells, acinar cells may also be the origin of PDAC. During pancreatitis or combined with activating KRasG12 D mutation, acinar cells lose their cellular identity and undergo a transdifferentiation process called acinarto-ductal-metaplasia(ADM), forming duct cells which may then transform into pancreatic intraepithelial neoplasia(Pan IN) and eventually PDAC. During ADM, the activation of mitogen-activated protein kinases, Wnt, Notch and phosphatidylinositide 3-kinases/Akt signaling inhibits the transcription of acinar-specific genes, including Mist and amylase, but promotes the expression of ductal genes, such as cytokeratin-19. Inhibition of this transdifferentiation process hinders the development of Pan IN and PDAC. In addition, the transdifferentiated cells regain acinar identity, indicating ADM may be a reversible process. This provides a new therapeutic direction in treating PDAC through cancer reprogramming. Many studies have already demonstrated the success of switching Pan IN/PDAC back to normal cells through the use of PD325901, the expression of E47, and the knockdown of Dickkopf-3. In this review, we discuss the signaling pathways involved in ADM and the therapeutic potential of targeting reprogramming in order to treat PDAC.展开更多
BACKGROUND:Acute pancreatitis is an acute inflammatory process of the pancreas that frequently involves peripancreatic tissues and at times remote organ systems.For a long time,the etiology and pathogenesis of acute p...BACKGROUND:Acute pancreatitis is an acute inflammatory process of the pancreas that frequently involves peripancreatic tissues and at times remote organ systems.For a long time,the etiology and pathogenesis of acute pancreatitis has been intensively investigated worldwide,but the pathogenetic theories are controversial.The integrity of the pancreatic duct-acinar system might play an important role in the pathogenesis of this disease.DATA SOURCES:Web of Science and PubMed databases were searched for published studies(between January 1966 and June 2009)to identify relevant articles using the keywords'acinar hyperstimulation','pathogenesis','acute pancreatitis','pancreatic duct-acinar system',and'pancreatic duct pressure'.Most of the relevant articles were reviewed.RESULTS:From critical reading of the relevant articles,we found that the underlying mechanisms involved in the pathogenesis of acute pancreatitis are still under debate and ill-understood.On the basis of the relevant studies,we propose a hypothesis for the pathogenesis of acute pancreatitis,in which the integrity of the pancreatic duct-acinar system plays an essential role in the onset and progression of various forms of the disease.CONCLUSIONS:In our hypothesis,pancreatic duct obstruction and hyperstimulation of the exocrine pancreas are preconditions for the onset of acute pancreatitis;under the common conditions of pancreatic duct obstruction and acinar hyperstimulation,acute pancreatitis arises and develops.This may be an important common pathophysiological mechanism causing various forms of acute pancreatitis.(Hepntobiliary Pancreat Dis Int 2010;9:242-247)展开更多
In October 2009, a 71-year-old female was diagnosed with a cystic tumor in the tail of the pancreas with an irregular dilatation of the main pancreatic duct in the body and tail of the pancreas. A distal pancreatectom...In October 2009, a 71-year-old female was diagnosed with a cystic tumor in the tail of the pancreas with an irregular dilatation of the main pancreatic duct in the body and tail of the pancreas. A distal pancreatectomy with splenectomy, and partial resection of the duodenum, jejunum and transverse colon was performed. In March 2011, a follow-up computed tomography scan showed a low density mass at the head of the remnant pancreas. We diagnosed it as a recurrence of the tumor and performed a total pancreatectomy for the remnant pancreas. In the histological evaluation of the resected specimen of the distal pancreas, the neoplastic cells formed an acinar and papillary structure that extended into the main pancreatic duct. Mucin5AC, α1-antitrypsin (α-AT) and carcinoembryonic antigen (CEA) were detected in the tumor cells by immunohistochemistry. In the resected head of the pancreas, the tumor was composed of both acinar and ductal elements with a mottled pattern. The proportions of each element were approximately 40% and 60%, respectively. Strongly positive α-AT cells were detected in the acinar element. Some tumor cells were also CEA positive. However, the staining for synaptophysin and chromogranin A was negative in the tumor cells. Ultimately, we diagnosed the tumor as a recurrence of mixed acinar-ductal carcinoma in the remnant pancreas. In conclusion, we report here a rare case of repeated pancreatic resection for multicentric lesions of mixed acinar-ductal carcinoma of the pancreas.展开更多
Pancreatitis is an increasingly common and sometimes severe disease that lacks a specific therapy. The pathogenesis of pancreatitis is still not well understood. Calcium (Ca<sup>2+</sup>) is a versatile ca...Pancreatitis is an increasingly common and sometimes severe disease that lacks a specific therapy. The pathogenesis of pancreatitis is still not well understood. Calcium (Ca<sup>2+</sup>) is a versatile carrier of signals regulating many aspects of cellular activity and plays a central role in controlling digestive enzyme secretion in pancreatic acinar cells. Ca<sup>2+</sup> overload is a key early event and is crucial in the pathogenesis of many diseases. In pancreatic acinar cells, pathological Ca<sup>2+</sup> signaling (stimulated by bile, alcohol metabolites and other causes) is a key contributor to the initiation of cell injury due to prolonged and global Ca<sup>2+</sup> elevation that results in trypsin activation, vacuolization and necrosis, all of which are crucial in the development of pancreatitis. Increased release of Ca<sup>2+</sup> from stores in the intracellular endoplasmic reticulum and/or increased Ca<sup>2+</sup> entry through the plasma membrane are causes of such cell damage. Failed mitochondrial adenosine triphosphate (ATP) production reduces re-uptake and extrusion of Ca<sup>2+</sup> by the sarco/endoplasmic reticulum Ca<sup>2+</sup>-activated ATPase and plasma membrane Ca<sup>2+</sup>-ATPase pumps, which contribute to Ca<sup>2+</sup> overload. Current findings have provided further insight into the roles and mechanisms of abnormal pancreatic acinar Ca<sup>2+</sup> signals in pancreatitis. The lack of available specific treatments is therefore an objective of ongoing research. Research is currently underway to establish the mechanisms and interactions of Ca<sup>2+</sup> signals in the pathogenesis of pancreatitis.展开更多
AIM:To distinguish acinar cell carcinoma(ACC)from pancreatic adenocarcinoma(AC)by comparing their computed tomography findings.METHODS:Patients with ACC and AC were identified on the basis of results obtained using su...AIM:To distinguish acinar cell carcinoma(ACC)from pancreatic adenocarcinoma(AC)by comparing their computed tomography findings.METHODS:Patients with ACC and AC were identified on the basis of results obtained using surgically resected pancreatectomy specimens.The preoperative computer tomographic images of 6 acinar cell carcinoma patients and 67 pancreatic adenocarcinoma patients in 4 phases(non-contrast,arterial,portal venous,and delayed phase)were compared.The scan delay times were 40,70,and 120 s for each contrast-enhanced phase.The visual pattern,tomographic attenuation value,and time attenuation curve were assessed and compared between AC and ACC cases using the 2test,Wilcoxon signed-rank test,and Mann Whitney U test.RESULTS:The adenocarcinomas tended to be hypodense in all 4 phases.The acinar cell carcinomas also tended to be hypodense in the 3 contrast-enhancedphases,although their computed tomographic attenuation values were higher.Further,5 of the 6 acinar cell carcinomas(83%)were isodense in the non-contrast phase.The time attenuation curve of the adenocarcinomas showed a gradual increase through the 4 phases,and all adenocarcinomas showed peak enhancement during the delayed phase.The time attenuation curve of the acinar cell carcinomas showed peak enhancement during the portal venous phase in 4 cases and during the arterial phase in 2 cases.None of the 6 acinar cell carcinomas showed peak enhancement during the delayed phase.CONCLUSION:The tumor density in the non-contrast phase and time attenuation curve pattern clearly differ between acinar cell carcinomas and adenocarcinomas,and multidetector-row computed tomography can thus distinguish these tumors.展开更多
Pancreatic carcinomas with acinar differentiation are rare,accounting for 1%-2% of adult pancreatic tumors; they include pancreatic acinar cell carcinoma(PACC),pancreatoblastoma,and carcinomas of mixed differentiation...Pancreatic carcinomas with acinar differentiation are rare,accounting for 1%-2% of adult pancreatic tumors; they include pancreatic acinar cell carcinoma(PACC),pancreatoblastoma,and carcinomas of mixed differentiation. Patients with PACC have a prognosis better than pancreatic ductal adenocarcinomas but worse than pancreatic neuroendocrine tumors. Reports of overall survival range from 18 to 47 mo. A literature review on PACCs included comprehensive genomic profiling and whole exome sequencing on a series of more than 70 patients as well as other diagnostic studies including immunohistochemistry. Surgical resection of PACC is the preferred treatment for localized and resectable tumors. The efficacy of adjuvant treatment is unclear. Metastatic PACCs are generally not curable and treated with systemic chemotherapy. They are moderately responsive to chemotherapy with different regimens showing various degrees of response in case reports/series. Most of these regimens were developed to treat patients with pancreatic ductal adenocarcinomas or colorectal adenocarcinomas. Review of PACC's molecular profiling showed a number of gene alterations such as: SMAD4,BRAF,BRCA2,TP53,RB1,MEN1,JAK-1,BRCA-1,BRCA-2,and DNA mismatch repair abnormalities. PACCs had multiple somatic mutations with some targetable with available drugs. Therefore,molecular profiling of PACC should be an option for patients with refractory PACC.展开更多
Pancreatic acinar cells are secretory cells whose main function is to synthesize, store and f inally release digestive enzymes into the duodenum. However, in response to noxious stimuli, acinar cells behave like real ...Pancreatic acinar cells are secretory cells whose main function is to synthesize, store and f inally release digestive enzymes into the duodenum. However, in response to noxious stimuli, acinar cells behave like real inflammatory cells because of their ability to activate signalling transduction pathways involved in the expression of inflammatory mediators. Mediated by the kinase cascade, activation of Nuclear factor-κB, Activating factor-1 and Signal transducers and activators of transcription transcription factors has been demonstrated in acinar cells, resulting in overexpression of inflammatory genes. In turn, kinase activity is down-regulated by protein phosphatases and the f inal balance between kinase and phosphatase activity will determine the capability of the acinar cells to produce inflammatory factors. The kinase/ phosphatase pair is a redox-sensitive system in which kinase activation overwhelms phosphatase activity under oxidant conditions. Thus, the oxidative stress developed within acinar cells at early stages of acute pancreatitis triggers the activation of signalling pathways involved in the up-regulation of cytokines, chemokines and adhesion molecules. In this way, acinar cells trigger the release of the f irst inflammatory signals which can mediate the activation and recruitment of circulating inflammatorycells into the injured pancreas. Accordingly, the role of acinar cells as promoters of the inflammatory response in acute pancreatitis may be considered. This concept leads to amplifying the focus from leukocyte to acinar cells themselves, to explain the local inflammation in early pancreatitis.展开更多
Acute pancreatitis (AP) is an inflammatory disorder of pancreatic tissue initiated in injured acinar cells. Severe AP remains a significant challenge due to the lack of effective treatment. The widely-accepted autodig...Acute pancreatitis (AP) is an inflammatory disorder of pancreatic tissue initiated in injured acinar cells. Severe AP remains a significant challenge due to the lack of effective treatment. The widely-accepted autodigestion theory of AP is now facing challenges, since inhibiting protease activation has negligible effectiveness for AP treatment despite numerous efforts. Furthermore, accumulating evidence supports a new concept that malfunction of a self-protective mechanism, the unfolded protein response(UPR), is the driving force behind the pathogenesis of AP. The UPR is induced by endoplasmic reticulum(ER) stress, a disturbance frequently found in acinar cells, to prevent the aggravation of ER stress that can otherwise lead to cell injury. In addition, the UPR's signaling pathways control NFκB activation and autophagy flux, and these dysregulations cause acinar cell inflammatory injury in AP, but with poorly understood mechanisms. We therefore summarize the protective role of the UPR in AP, propose mechanistic models of how inadequate UPR could promote NFκB's pro-inflammatory activity and impair autophagy's protective function in acinar cells, and discuss its relevance to current AP treatment. We hope that insight provided in this review will help facilitate the research and management of AP.展开更多
AIM To investigate the effects of combined use of emodin and baicalein(CEB) at the cellular and organism levelsin severe acute pancreatitis(SAP) and explore the underlying mechanism.METHODS SAP was induced by retrogra...AIM To investigate the effects of combined use of emodin and baicalein(CEB) at the cellular and organism levelsin severe acute pancreatitis(SAP) and explore the underlying mechanism.METHODS SAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in 48 male SD rats. Pancreatic histopathology score, serum amylase activity, and levels of tumour necrosis factor alpha(TNf-α), interleukin 6(IL-6), and IL-10 were determined to assess the effects of CEB at 12 h after the surgery. The rat pancreatic acinar cells were isolated from healthy male SD rats using collagenase. The cell viability, cell ultrastructure, intracellular free Ca2+ concentration, and inositol(1,4,5)-trisphosphate receptor(IP3 R) expression were investigated to assess the mechanism of CEB.RESULTS Pancreatic histopathology score(2.07 ± 1.20 vs 6.84 ± 1.13, P < 0.05) and serum amylase activity(2866.2 ± 617.7 vs 5241.3 ± 1410.0, P < 0.05) were significantly decreased in the CEB(three doses) treatment group compared with the SAP group(2.07 ± 1.20 vs 6.84 ± 1.13, P < 0.05). CEB dose-dependently reduced the levels of the pro-inflammatory cytokines IL-6(466.82 ± 48.55 vs 603.50 ± 75.53, P < 0.05) and TNF-α(108.04 ± 16.10 vs 215.56 ± 74.67, P < 0.05) and increased the level of the anti-inflammatory cytokine IL-10(200.96 ± 50.76 vs 54.18 ± 6.07, P < 0.05) compared with those in the SAP group. CEB increased cell viability, inhibited cytosolic Ca2+ concentration, and significantly ameliorated intracellular vacuoles and IP3 m RNA expression compared with those in the SAP group(P < 0.05). There was a trend towards decreased IP3 R protein in the CEB treatment group; however, it did not reach statistical significance(P > 0.05).CONCLUSION These results at the cellular and organism levels reflect a preliminary mechanism of CEB in SAP and indicate that CEB is a suitable approach for SAP treatment.展开更多
The expression of micro RNA-19b（mi R-19b） in acute necrotizing pancreatitis（ANP） and its functional role in acinar cell necrosis of SD rats were investigated. Twelve SD rats were divided into two groups randomly, ...The expression of micro RNA-19b（mi R-19b） in acute necrotizing pancreatitis（ANP） and its functional role in acinar cell necrosis of SD rats were investigated. Twelve SD rats were divided into two groups randomly, including control group and ANP group. The rat ANP models were established by intraperitoneal injection of L-arginine（2400 mg/kg body weight）, and equal volume of 0.9% Na Cl was injected in the control group. Mi RNA chip assay was performed to examine the expression of mi RNAs in the pancreas in two different groups. Besides, to further explore the role of mi R-19 b in ANP in vitro, taurolithocholic acid 3-sulfate disodium salt（TLC-S）（200 μmol/L） was administrated to treat the rat pancreatic acinar cell line, AR42 J, for establishing the ANP cells model. The quantitative real-time PCR（q RT-PCR） was adopted to measure the mi R-19 b expression. Moreover, the mimic mi RNA, mi RNA antisense oligonucleotide（AMO） and control vector were used to transfect AR42 J cells, the expression of mi R-19 b was confirmed by q RT-PCR and the necrotizing rate of AR42 J cells was detected with AO/EB method. The expression of mi R-19 b was significantly higher in ANP group than in control group as displayed by the mi RNA chip assay. Furthermore, after inducing necrosis of AR42 J cells in vitro, the expression of mi R-19 b was significantly increased by 2.51±0.14 times in comparison with the control group. As revealed by q RT-PCR assay, the expression of mi R-19 b was 5.94±0.95 times higher in the mimic mi RNA group than in the control vector group, companied with an obviously increased acinar cell necrotizing rate（50.3%±1.5% vs. 39.6%±2.3%, P〈0.05）. Moreover, the expression of mi R-19 b in the mi RNA AMO group was 0.38±0.15 times lower than in the control vector group, and the cell necrosis rate was much lower accordingly（23.1%±3.3% vs. 39.6%±2.3%, P〈0.05）. Besides, there was no significant difference between the control vector cells and the cells without treatment（P〈0.05）. The expression of mi R-19 b was significantly induced in ANP. In addition, up-regulation of mi R-19 b could promote the necrosis of pancreatic acinar cells and mi R-19 b deficiency could decrease the rate of pancreatic acinar cell necrosis.展开更多
The current literature does not support the usefulness of clinical markers on predicting which patients with atypical small acinar proliferation （ASAP） are more likely to progress to prostate cancer （PCa）. Androge...The current literature does not support the usefulness of clinical markers on predicting which patients with atypical small acinar proliferation （ASAP） are more likely to progress to prostate cancer （PCa）. Androgens have long been considered to be the potential risk factors for PCa. However, the role of testosterone is controversial. The present study aims to analyze the relationship between serum testosterone （TS） levels and the diagnosis of PCa after a first prostate biopsy in patients affected by ASAP. This retrospective study included 143 patients diagnosed with ASAP in an initial transrectal ultrasound-guided prostate biopsy for suspicious PCa according to the European Association of Urology guidelines. Their TS levels, age, PSA, prostate volume, digital rectal examination, and prostate biopsy Gleason score （GS） were collected retrospectively for statistical analysis. All patients included in the study had a second biopsy and were suitable for further analysis. Re-biopsy was carried out 3-6 months after the first diagnosis of ASAP. Low and normal TS groups were composed of 29 （20.3%） and 114 （79.7%） patients, respectively. The diagnosis of the second biopsy was ASAP in 25.2% and PCa in 36.4% of patients. The comparison between patients with PCa and those with negative or an ASAP result in the second biopsy reported that men with cancer had significantly higher levels of TS （P 〈 0.001）. However, there was no statistically significant association between GS postbiopsy and TS （P = 0.324）. Our experience demonstrated that eugonadal patients may be a clinical risk factor for the diagnosis of PCa on re-biopsy after ASAP diagnosis than hypogonadal.展开更多
Acinar cell carcinoma(ACC)is a rare pancreatic malignancy with distinctive clinical,molecular,and morphological features.The long-term survival of ACC patients is substantially superior to that of pancreatic adenocarc...Acinar cell carcinoma(ACC)is a rare pancreatic malignancy with distinctive clinical,molecular,and morphological features.The long-term survival of ACC patients is substantially superior to that of pancreatic adenocarcinoma patients.As there are no significant patient series about ACCs,our understanding of this illness is mainly based on case reports and limited patient series.Surgical resection is the treatment of choice for patients with the disease restricted to one organ;however,with recent breakthroughs in precision medicine,medicines targeting the one-of-a-kind molecular profile of ACC are on the horizon.There are no standard treatment protocols available for people in which a total surgical resection to cure the condition is not possible.As a result of shared genetic alterations,ACCs are chemosensitive to agents with activity against pancreatic adenocarcinomas and colorectal carcinomas.The role of neoadjuvant or adjuvant chemoradiotherapy has not been established.This article aims to do a comprehensive literature study and present the most recent information on acinar cell cancer.展开更多
A peptide hormone, ghrelin, recognized for its role in the regulation of nitric oxide production has emerged as an important modulator of oral mucosal inflammatory responses to periodontopathic bacterium, P. gingivali...A peptide hormone, ghrelin, recognized for its role in the regulation of nitric oxide production has emerged as an important modulator of oral mucosal inflammatory responses to periodontopathic bacterium, P. gingivalis. As cSrc kinase plays a major role in controlling the activity of nitric oxide synthase (NOS) system, in this study we investigated the influence of P. gingivalis LPS on the processes of Src activation in rat sublingual gland acinar cells. The LPS-induced enhancement in the activity of inducible (i) iNOS and the impairment in constitutive (c) cNOS were reflected in the suppression in cSrc activity and the extent of its phosphorylation at Tyr416. Further, we show that the countering effect of ghrelin on the LPS-induced changes in cSrc activity and the extent of its phosphorylation was accompanied by a marked reduction in iNOS and the increase in cNOS activation through phosphorylation at Ser1179. Moreover, the effect of ghrelin on cSrc activation was associated with the kinase S-nitrosylation that was susceptible to the blockage by cNOS inhibition. Our findings suggest that P. gingivalis-induced up-regulation in iNOS leads to disturbances in cNOS phosphorylation that exerts the detrimental effect on the processes of cSrc activation through cNOS mediated S-nitrosylation. We also show that the effect of ghrelin on P. gingivalis-induced inflammatory changes are manifested in the enhancement in cSrc activation through S-nitrosylation and the increase in its phosphorylation at Tyr416.展开更多
AIM: To investigate the effect of Tetrandrine (Tet) on LPS-induced NF-κB activation and cell injury in pancreatic acinar cells and to explore the mechanism of Tetrandrine preventing LPS-induced acinar cell injury. ME...AIM: To investigate the effect of Tetrandrine (Tet) on LPS-induced NF-κB activation and cell injury in pancreatic acinar cells and to explore the mechanism of Tetrandrine preventing LPS-induced acinar cell injury. METHODS: Male rat pancreatic acinar cells were isolated by collagenase digestion, then exposed to LPS (10 mg/L), Tet (50μmol/L, 100μmol/L) or normal media. At different time point (30 min, 1 h, 4 h, 10 h) after treatment with the agents, cell viability was determined by MTT, the product and nuclear translocation of subunit p65 of NF-κB was visualized by immunofluorescence staining and nuclear protein was extracted to perform EMSA which was used to assay the NF-κB binding activity. RESULTS: LPS induced cell damage directly in a time dependent manner and Tet attenuated LPS-induced cell damage (50μmol/L, P < 0.05; 100μmol/L, P < 0.01). NF-κB p65 immunofluorescence staining in cytoplasm increased and began showing its nuclear translocation within 30 min and the peak was shown at 1 h of LPS 10 mg/L treatment. NF-κB DNA binding activity showed the same alteration pattern as p65 immunofluorescence staining. In Tet group, the immunofluorescence staining in cytoplasm and nuclear translocation of NF-κB were inhibited significantly. CONCLUSION: NF-κB activation is an important early event that may contribute to inflammatory responses and cell injury in pancreatic acinar cells. Tet possesses the protective effect on LPS-induced acinar cell injury by inhibiting NF-κB activation.展开更多
BACKGROUND:Acinar cell carcinoma (ACC) is a rare malignancy of the pancreas arising from acinar cells.Unlike ductal adenocarcinoma,this tumor rarely presents with pancreatitis.METHODS:We present a case of ACC associat...BACKGROUND:Acinar cell carcinoma (ACC) is a rare malignancy of the pancreas arising from acinar cells.Unlike ductal adenocarcinoma,this tumor rarely presents with pancreatitis.METHODS:We present a case of ACC associated with chronic calcifying pancreatitis,and a review of the literature focusing on diagnosis and management.RESULTS:A 43-year-old man was proposed for Wirsungojejunal derivation for chronic pancreatitis.Histopathological examination of the tissue extracted revealed an ACC.Duodenopancreatectomy was performed.Six months postoperatively,the patient developed hepatic metastasis and was treated with gemcitabine as palliative chemotherapy.CONCLUSIONS:The clinical presentation of ACC of the pancreas is not specific and the tumor can be underdiagnosed when associated with chronic pancreatitis.Data regarding course,treatment,and prognosis of this tumor are generally lacking.展开更多
Background: Previous studies have provided conflicting results regarding whether the serum ghrelin concentration can reflect the severity of acute pancreatitis(AP). The present study examined the correlation between t...Background: Previous studies have provided conflicting results regarding whether the serum ghrelin concentration can reflect the severity of acute pancreatitis(AP). The present study examined the correlation between the serum ghrelin concentration and AP severity in animal models and investigated whether altered ghrelin expression in pancreatic acinar cells influences IKK β/NF-κ B signaling and pro-inflammatory cytokine production. Methods: Mild or severe AP was induced in rats by intraperitoneal injection of cerulein or retrograde cholangiopancreatic duct injection of sodium taurocholate, respectively. After successful model induction, serum ghrelin, tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) concentrations were determined by enzyme-linked immunosorbent assay, and IKK β/NF-κ B activation was assessed by immunohistochemistry. Subsequently, stable overexpression or knockdown of ghrelin in AR42 J cells was achieved by lentiviral transfection. After transfected cells and control cells were treated with cerulein for 24 h, the TNF-αand IL-1 β levels in the supernatants were determined by enzyme-linked immunosorbent assay, and the expression levels of p-p65, IKK β, and p-IKK β were detected by Western blotting. Results: In rat AP models, AP severity was correlated with increased IKK β/NF-κ B activation, proinflammatory cytokine production, and ghrelin secretion. The levels of pro-inflammatory cytokines TNF-αand IL-1 β as well as IKK β/NF-κ B signaling activity were increased upon knockdown of ghrelin in the AP acinar cell model and decreased with ghrelin overexpression. Conclusions: Serum ghrelin is related to the severity of AP. Ghrelin may play a protective role in the pathogenesis of AP by inhibiting the pro-inflammatory cytokines and the activation of the IKK β/NF-κ B signaling pathway.展开更多
Cell proliferation is an important process in life for growth of normal and cancer cells. The signal transduction pathways activated during this process are strictly regulated. This editorial focuses on the role of ni...Cell proliferation is an important process in life for growth of normal and cancer cells. The signal transduction pathways activated during this process are strictly regulated. This editorial focuses on the role of nicotine, a mitogen, in the induction of signaling pathways resulting in proliferation of pancreatic tumor cells and compares these events with those in normal acinar cells isolated from the rat pancreas. The data shows striking similarities between these two cellular systems. In addition, the editorial reviews very recent literature of the contribution of MAPK signaling in cell lines associated with human diseases. A prospective cellular model of nicotine induced activation of MAPK cascade is presented.展开更多
文摘BACKGROUND Acinar cystic transformation(ACT)of the pancreas is a rare non-neoplastic transformation of the pancreas.Adult women are the majority of patients with ACT,but few cases have been reported in pediatric patients.Given that there are currently no guidelines for the treatment of ACT,current treatment is based primarily on expert opinions and clinical experiences.Here,we report the case of the youngest child with ACT to date.Additionally,a literature review on pediatric ACT cases was performed to summarize previous clinical experience and treatment methods.CASE SUMMARY A 1-year-old Chinese girl presented with progressive abdominal distension for 6 months.A detailed consultation revealed an uneventful history.The patient showed no signs of fever or abdominal pain and had a good appetite and normal feces.A mass of about 20 cm×10 cm×10 cm in size was detected in the abdomen.Both abdominal ultrasound and computed tomography examination revealed a multilocular cystic mass about 21.7 cm×16.8 cm×8.9 cm in size.At first,due to the large size and the possible retroperitoneal origin of the cyst,a total resection of the lesion was not possible.A single-port laparoscopic lymphangioma puncture and Pingyangmycin injection were performed in March 2023.One month after surgery,the abdominal cyst rapidly enlarged to its pre-operative size.After consulting with the experts in the angiology department and interventional department,sclerotherapy combined with oral sirolimus was performed in May 2023.After confirming that the tumor was not sensitive to sclerotherapy combined with oral sirolimus,our surgical team performed tumor reduction in August 2023.This surgery confirmed that the polycystic mass originated from the head of the pancreas,and pathological and immunohistochemical findings diagnosed pancreatic ACT.The patient showed no signs of cyst lesions after 6 months of follow-up and remains in good health up to the time of this report.CONCLUSION ACT is a rare non-neoplastic transformation of the pancreas,more rarely seen in children.Manifestation and examinations show no specificity for diagnosis,and final diagnosis is mainly based on histological findings.To reach a specific diagnosis and rule out malignancy is a priority in clinical practice,and repeated biopsy or radical surgery should be considered before malignancy is ruled out.However,once a diagnosis of ACT is made,a conser-vative treatment with consecutive follow-up is recommended until symptoms present or obvious enlargement occurs because ACT is considered a slow-growing and benign tumor.
基金supported by a grant from the National Natural Science Foundation of China(82202974).
文摘To the Editor:Pancreatic acinar cell carcinoma(PACC),with primary compo-nent similar to acinar cells,represents merely 1%-2%of pancreatic exocrine neoplasms[1].As a high-grade malignancy,PACC has the potential to manifest in any anatomical region of the pancreas,while mostly in the head of the pancreas[2].The initial symptoms of PACC may not be obvious.Upon diagnosis,the tumor typi-cally manifests as a substantial size,resulting in compression of adjacent organs and subsequent non-specific gastrointestinal mani-festations.These complications encompass abdominal pain,nausea,diarrhea,and weight loss[3].Nevertheless,the incidence of bile duct obstruction and jaundice is relatively modest.Despite being classified as an aggressive tumor,PACC exhibits a slightly slower disease progression compared to pancreatic ductal adenocarcinoma(PDAC).Currently,the median survival of PACC ranges from 18 to 47 months[4].Here,we presented a unique occurrence of PACC with liver metastases,aiming to enhance comprehension of the disease and diminish the probability of misdiagnosis.
基金support from Fonds de Recherche du Québec Santé(FRQS,grant no.281271)support from FRQS doctoral award #304367funding from CFI,Rheolution Inc.,and Investissement Québec.
文摘Xerostomia(dry mouth)is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren’s syndrome,with no permanent cure existing for this debilitating condition.To this end,in vitro platforms are needed to test therapies directed at salivary(fluid-secreting)cells.However,since these are highly differentiated secretory cells,the maintenance of their differentiated state while expanding in numbers is challenging.In this study,the efficiency of three reversible thermo-ionically crosslinked gels:(1)alginate–gelatin(AG),(2)collagen-containing AG(AGC),and(3)hyaluronic acid-containing AG(AGHA),to recapitulate a native-like environment for human salivary gland(SG)cell expansion and 3D spheroid formation was compared.Although all gels were of mechanical properties comparable to human SG tissue(~11 kPa)and promoted the formation of 3D spheroids,AGHA gels produced larger(>100 cells/spheroid),viable(>93%),proliferative,and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins(aquaporin-5,NKCC1,ZO-1,α-amylase)for 14 days in culture.Moreover,the spheroids responded to agonist-induced stimulation by increasingα-amylase secretory granules.Here,we propose alternative lowcost,reproducible,and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact,highly viable 3D-SG spheroids.
基金Supported by the General Research Fund,Research Grants Council of Hong Kong,No.CUHK462211,No.CUHK462713 and No.14102714the National Natural Science Foundation of China,No.81101888 and No.8142730
文摘Pancreatic ductal adenocarcinoma(PDAC) is a common pancreatic cancer and the fourth leading cause of cancer death in the United States. Treating this life-threatening disease remains challenging due to the lack of effective prognosis, diagnosis and therapy. Apart from pancreatic duct cells, acinar cells may also be the origin of PDAC. During pancreatitis or combined with activating KRasG12 D mutation, acinar cells lose their cellular identity and undergo a transdifferentiation process called acinarto-ductal-metaplasia(ADM), forming duct cells which may then transform into pancreatic intraepithelial neoplasia(Pan IN) and eventually PDAC. During ADM, the activation of mitogen-activated protein kinases, Wnt, Notch and phosphatidylinositide 3-kinases/Akt signaling inhibits the transcription of acinar-specific genes, including Mist and amylase, but promotes the expression of ductal genes, such as cytokeratin-19. Inhibition of this transdifferentiation process hinders the development of Pan IN and PDAC. In addition, the transdifferentiated cells regain acinar identity, indicating ADM may be a reversible process. This provides a new therapeutic direction in treating PDAC through cancer reprogramming. Many studies have already demonstrated the success of switching Pan IN/PDAC back to normal cells through the use of PD325901, the expression of E47, and the knockdown of Dickkopf-3. In this review, we discuss the signaling pathways involved in ADM and the therapeutic potential of targeting reprogramming in order to treat PDAC.
基金supported by a grant from the National Natural Science Foundation of China(No.30830100)
文摘BACKGROUND:Acute pancreatitis is an acute inflammatory process of the pancreas that frequently involves peripancreatic tissues and at times remote organ systems.For a long time,the etiology and pathogenesis of acute pancreatitis has been intensively investigated worldwide,but the pathogenetic theories are controversial.The integrity of the pancreatic duct-acinar system might play an important role in the pathogenesis of this disease.DATA SOURCES:Web of Science and PubMed databases were searched for published studies(between January 1966 and June 2009)to identify relevant articles using the keywords'acinar hyperstimulation','pathogenesis','acute pancreatitis','pancreatic duct-acinar system',and'pancreatic duct pressure'.Most of the relevant articles were reviewed.RESULTS:From critical reading of the relevant articles,we found that the underlying mechanisms involved in the pathogenesis of acute pancreatitis are still under debate and ill-understood.On the basis of the relevant studies,we propose a hypothesis for the pathogenesis of acute pancreatitis,in which the integrity of the pancreatic duct-acinar system plays an essential role in the onset and progression of various forms of the disease.CONCLUSIONS:In our hypothesis,pancreatic duct obstruction and hyperstimulation of the exocrine pancreas are preconditions for the onset of acute pancreatitis;under the common conditions of pancreatic duct obstruction and acinar hyperstimulation,acute pancreatitis arises and develops.This may be an important common pathophysiological mechanism causing various forms of acute pancreatitis.(Hepntobiliary Pancreat Dis Int 2010;9:242-247)
文摘In October 2009, a 71-year-old female was diagnosed with a cystic tumor in the tail of the pancreas with an irregular dilatation of the main pancreatic duct in the body and tail of the pancreas. A distal pancreatectomy with splenectomy, and partial resection of the duodenum, jejunum and transverse colon was performed. In March 2011, a follow-up computed tomography scan showed a low density mass at the head of the remnant pancreas. We diagnosed it as a recurrence of the tumor and performed a total pancreatectomy for the remnant pancreas. In the histological evaluation of the resected specimen of the distal pancreas, the neoplastic cells formed an acinar and papillary structure that extended into the main pancreatic duct. Mucin5AC, α1-antitrypsin (α-AT) and carcinoembryonic antigen (CEA) were detected in the tumor cells by immunohistochemistry. In the resected head of the pancreas, the tumor was composed of both acinar and ductal elements with a mottled pattern. The proportions of each element were approximately 40% and 60%, respectively. Strongly positive α-AT cells were detected in the acinar element. Some tumor cells were also CEA positive. However, the staining for synaptophysin and chromogranin A was negative in the tumor cells. Ultimately, we diagnosed the tumor as a recurrence of mixed acinar-ductal carcinoma in the remnant pancreas. In conclusion, we report here a rare case of repeated pancreatic resection for multicentric lesions of mixed acinar-ductal carcinoma of the pancreas.
基金Supported by grants from the National Natural Science Foundation of China No.30171167,No.30901945the Specialized Research Fund for the Doctoral Program of Higher Education No.20130201130009
文摘Pancreatitis is an increasingly common and sometimes severe disease that lacks a specific therapy. The pathogenesis of pancreatitis is still not well understood. Calcium (Ca<sup>2+</sup>) is a versatile carrier of signals regulating many aspects of cellular activity and plays a central role in controlling digestive enzyme secretion in pancreatic acinar cells. Ca<sup>2+</sup> overload is a key early event and is crucial in the pathogenesis of many diseases. In pancreatic acinar cells, pathological Ca<sup>2+</sup> signaling (stimulated by bile, alcohol metabolites and other causes) is a key contributor to the initiation of cell injury due to prolonged and global Ca<sup>2+</sup> elevation that results in trypsin activation, vacuolization and necrosis, all of which are crucial in the development of pancreatitis. Increased release of Ca<sup>2+</sup> from stores in the intracellular endoplasmic reticulum and/or increased Ca<sup>2+</sup> entry through the plasma membrane are causes of such cell damage. Failed mitochondrial adenosine triphosphate (ATP) production reduces re-uptake and extrusion of Ca<sup>2+</sup> by the sarco/endoplasmic reticulum Ca<sup>2+</sup>-activated ATPase and plasma membrane Ca<sup>2+</sup>-ATPase pumps, which contribute to Ca<sup>2+</sup> overload. Current findings have provided further insight into the roles and mechanisms of abnormal pancreatic acinar Ca<sup>2+</sup> signals in pancreatitis. The lack of available specific treatments is therefore an objective of ongoing research. Research is currently underway to establish the mechanisms and interactions of Ca<sup>2+</sup> signals in the pathogenesis of pancreatitis.
文摘AIM:To distinguish acinar cell carcinoma(ACC)from pancreatic adenocarcinoma(AC)by comparing their computed tomography findings.METHODS:Patients with ACC and AC were identified on the basis of results obtained using surgically resected pancreatectomy specimens.The preoperative computer tomographic images of 6 acinar cell carcinoma patients and 67 pancreatic adenocarcinoma patients in 4 phases(non-contrast,arterial,portal venous,and delayed phase)were compared.The scan delay times were 40,70,and 120 s for each contrast-enhanced phase.The visual pattern,tomographic attenuation value,and time attenuation curve were assessed and compared between AC and ACC cases using the 2test,Wilcoxon signed-rank test,and Mann Whitney U test.RESULTS:The adenocarcinomas tended to be hypodense in all 4 phases.The acinar cell carcinomas also tended to be hypodense in the 3 contrast-enhancedphases,although their computed tomographic attenuation values were higher.Further,5 of the 6 acinar cell carcinomas(83%)were isodense in the non-contrast phase.The time attenuation curve of the adenocarcinomas showed a gradual increase through the 4 phases,and all adenocarcinomas showed peak enhancement during the delayed phase.The time attenuation curve of the acinar cell carcinomas showed peak enhancement during the portal venous phase in 4 cases and during the arterial phase in 2 cases.None of the 6 acinar cell carcinomas showed peak enhancement during the delayed phase.CONCLUSION:The tumor density in the non-contrast phase and time attenuation curve pattern clearly differ between acinar cell carcinomas and adenocarcinomas,and multidetector-row computed tomography can thus distinguish these tumors.
文摘Pancreatic carcinomas with acinar differentiation are rare,accounting for 1%-2% of adult pancreatic tumors; they include pancreatic acinar cell carcinoma(PACC),pancreatoblastoma,and carcinomas of mixed differentiation. Patients with PACC have a prognosis better than pancreatic ductal adenocarcinomas but worse than pancreatic neuroendocrine tumors. Reports of overall survival range from 18 to 47 mo. A literature review on PACCs included comprehensive genomic profiling and whole exome sequencing on a series of more than 70 patients as well as other diagnostic studies including immunohistochemistry. Surgical resection of PACC is the preferred treatment for localized and resectable tumors. The efficacy of adjuvant treatment is unclear. Metastatic PACCs are generally not curable and treated with systemic chemotherapy. They are moderately responsive to chemotherapy with different regimens showing various degrees of response in case reports/series. Most of these regimens were developed to treat patients with pancreatic ductal adenocarcinomas or colorectal adenocarcinomas. Review of PACC's molecular profiling showed a number of gene alterations such as: SMAD4,BRAF,BRCA2,TP53,RB1,MEN1,JAK-1,BRCA-1,BRCA-2,and DNA mismatch repair abnormalities. PACCs had multiple somatic mutations with some targetable with available drugs. Therefore,molecular profiling of PACC should be an option for patients with refractory PACC.
基金Supported by A grant from Insituto de Salud Carlos , Spain,PI08/0035
文摘Pancreatic acinar cells are secretory cells whose main function is to synthesize, store and f inally release digestive enzymes into the duodenum. However, in response to noxious stimuli, acinar cells behave like real inflammatory cells because of their ability to activate signalling transduction pathways involved in the expression of inflammatory mediators. Mediated by the kinase cascade, activation of Nuclear factor-κB, Activating factor-1 and Signal transducers and activators of transcription transcription factors has been demonstrated in acinar cells, resulting in overexpression of inflammatory genes. In turn, kinase activity is down-regulated by protein phosphatases and the f inal balance between kinase and phosphatase activity will determine the capability of the acinar cells to produce inflammatory factors. The kinase/ phosphatase pair is a redox-sensitive system in which kinase activation overwhelms phosphatase activity under oxidant conditions. Thus, the oxidative stress developed within acinar cells at early stages of acute pancreatitis triggers the activation of signalling pathways involved in the up-regulation of cytokines, chemokines and adhesion molecules. In this way, acinar cells trigger the release of the f irst inflammatory signals which can mediate the activation and recruitment of circulating inflammatorycells into the injured pancreas. Accordingly, the role of acinar cells as promoters of the inflammatory response in acute pancreatitis may be considered. This concept leads to amplifying the focus from leukocyte to acinar cells themselves, to explain the local inflammation in early pancreatitis.
文摘Acute pancreatitis (AP) is an inflammatory disorder of pancreatic tissue initiated in injured acinar cells. Severe AP remains a significant challenge due to the lack of effective treatment. The widely-accepted autodigestion theory of AP is now facing challenges, since inhibiting protease activation has negligible effectiveness for AP treatment despite numerous efforts. Furthermore, accumulating evidence supports a new concept that malfunction of a self-protective mechanism, the unfolded protein response(UPR), is the driving force behind the pathogenesis of AP. The UPR is induced by endoplasmic reticulum(ER) stress, a disturbance frequently found in acinar cells, to prevent the aggravation of ER stress that can otherwise lead to cell injury. In addition, the UPR's signaling pathways control NFκB activation and autophagy flux, and these dysregulations cause acinar cell inflammatory injury in AP, but with poorly understood mechanisms. We therefore summarize the protective role of the UPR in AP, propose mechanistic models of how inadequate UPR could promote NFκB's pro-inflammatory activity and impair autophagy's protective function in acinar cells, and discuss its relevance to current AP treatment. We hope that insight provided in this review will help facilitate the research and management of AP.
基金Supported by National Natural Science Foundation of China,No.30901945Science Research Foundation of Shaanxi Administration of Traditional Chinese Medicine,No.15-ZY029Science Research Foundation of the Second Affiliated Hospital of Xi’an Jiaotong University,No.RC(XM)201602
文摘AIM To investigate the effects of combined use of emodin and baicalein(CEB) at the cellular and organism levelsin severe acute pancreatitis(SAP) and explore the underlying mechanism.METHODS SAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in 48 male SD rats. Pancreatic histopathology score, serum amylase activity, and levels of tumour necrosis factor alpha(TNf-α), interleukin 6(IL-6), and IL-10 were determined to assess the effects of CEB at 12 h after the surgery. The rat pancreatic acinar cells were isolated from healthy male SD rats using collagenase. The cell viability, cell ultrastructure, intracellular free Ca2+ concentration, and inositol(1,4,5)-trisphosphate receptor(IP3 R) expression were investigated to assess the mechanism of CEB.RESULTS Pancreatic histopathology score(2.07 ± 1.20 vs 6.84 ± 1.13, P < 0.05) and serum amylase activity(2866.2 ± 617.7 vs 5241.3 ± 1410.0, P < 0.05) were significantly decreased in the CEB(three doses) treatment group compared with the SAP group(2.07 ± 1.20 vs 6.84 ± 1.13, P < 0.05). CEB dose-dependently reduced the levels of the pro-inflammatory cytokines IL-6(466.82 ± 48.55 vs 603.50 ± 75.53, P < 0.05) and TNF-α(108.04 ± 16.10 vs 215.56 ± 74.67, P < 0.05) and increased the level of the anti-inflammatory cytokine IL-10(200.96 ± 50.76 vs 54.18 ± 6.07, P < 0.05) compared with those in the SAP group. CEB increased cell viability, inhibited cytosolic Ca2+ concentration, and significantly ameliorated intracellular vacuoles and IP3 m RNA expression compared with those in the SAP group(P < 0.05). There was a trend towards decreased IP3 R protein in the CEB treatment group; however, it did not reach statistical significance(P > 0.05).CONCLUSION These results at the cellular and organism levels reflect a preliminary mechanism of CEB in SAP and indicate that CEB is a suitable approach for SAP treatment.
文摘The expression of micro RNA-19b（mi R-19b） in acute necrotizing pancreatitis（ANP） and its functional role in acinar cell necrosis of SD rats were investigated. Twelve SD rats were divided into two groups randomly, including control group and ANP group. The rat ANP models were established by intraperitoneal injection of L-arginine（2400 mg/kg body weight）, and equal volume of 0.9% Na Cl was injected in the control group. Mi RNA chip assay was performed to examine the expression of mi RNAs in the pancreas in two different groups. Besides, to further explore the role of mi R-19 b in ANP in vitro, taurolithocholic acid 3-sulfate disodium salt（TLC-S）（200 μmol/L） was administrated to treat the rat pancreatic acinar cell line, AR42 J, for establishing the ANP cells model. The quantitative real-time PCR（q RT-PCR） was adopted to measure the mi R-19 b expression. Moreover, the mimic mi RNA, mi RNA antisense oligonucleotide（AMO） and control vector were used to transfect AR42 J cells, the expression of mi R-19 b was confirmed by q RT-PCR and the necrotizing rate of AR42 J cells was detected with AO/EB method. The expression of mi R-19 b was significantly higher in ANP group than in control group as displayed by the mi RNA chip assay. Furthermore, after inducing necrosis of AR42 J cells in vitro, the expression of mi R-19 b was significantly increased by 2.51±0.14 times in comparison with the control group. As revealed by q RT-PCR assay, the expression of mi R-19 b was 5.94±0.95 times higher in the mimic mi RNA group than in the control vector group, companied with an obviously increased acinar cell necrotizing rate（50.3%±1.5% vs. 39.6%±2.3%, P〈0.05）. Moreover, the expression of mi R-19 b in the mi RNA AMO group was 0.38±0.15 times lower than in the control vector group, and the cell necrosis rate was much lower accordingly（23.1%±3.3% vs. 39.6%±2.3%, P〈0.05）. Besides, there was no significant difference between the control vector cells and the cells without treatment（P〈0.05）. The expression of mi R-19 b was significantly induced in ANP. In addition, up-regulation of mi R-19 b could promote the necrosis of pancreatic acinar cells and mi R-19 b deficiency could decrease the rate of pancreatic acinar cell necrosis.
文摘The current literature does not support the usefulness of clinical markers on predicting which patients with atypical small acinar proliferation （ASAP） are more likely to progress to prostate cancer （PCa）. Androgens have long been considered to be the potential risk factors for PCa. However, the role of testosterone is controversial. The present study aims to analyze the relationship between serum testosterone （TS） levels and the diagnosis of PCa after a first prostate biopsy in patients affected by ASAP. This retrospective study included 143 patients diagnosed with ASAP in an initial transrectal ultrasound-guided prostate biopsy for suspicious PCa according to the European Association of Urology guidelines. Their TS levels, age, PSA, prostate volume, digital rectal examination, and prostate biopsy Gleason score （GS） were collected retrospectively for statistical analysis. All patients included in the study had a second biopsy and were suitable for further analysis. Re-biopsy was carried out 3-6 months after the first diagnosis of ASAP. Low and normal TS groups were composed of 29 （20.3%） and 114 （79.7%） patients, respectively. The diagnosis of the second biopsy was ASAP in 25.2% and PCa in 36.4% of patients. The comparison between patients with PCa and those with negative or an ASAP result in the second biopsy reported that men with cancer had significantly higher levels of TS （P 〈 0.001）. However, there was no statistically significant association between GS postbiopsy and TS （P = 0.324）. Our experience demonstrated that eugonadal patients may be a clinical risk factor for the diagnosis of PCa on re-biopsy after ASAP diagnosis than hypogonadal.
文摘Acinar cell carcinoma(ACC)is a rare pancreatic malignancy with distinctive clinical,molecular,and morphological features.The long-term survival of ACC patients is substantially superior to that of pancreatic adenocarcinoma patients.As there are no significant patient series about ACCs,our understanding of this illness is mainly based on case reports and limited patient series.Surgical resection is the treatment of choice for patients with the disease restricted to one organ;however,with recent breakthroughs in precision medicine,medicines targeting the one-of-a-kind molecular profile of ACC are on the horizon.There are no standard treatment protocols available for people in which a total surgical resection to cure the condition is not possible.As a result of shared genetic alterations,ACCs are chemosensitive to agents with activity against pancreatic adenocarcinomas and colorectal carcinomas.The role of neoadjuvant or adjuvant chemoradiotherapy has not been established.This article aims to do a comprehensive literature study and present the most recent information on acinar cell cancer.
文摘A peptide hormone, ghrelin, recognized for its role in the regulation of nitric oxide production has emerged as an important modulator of oral mucosal inflammatory responses to periodontopathic bacterium, P. gingivalis. As cSrc kinase plays a major role in controlling the activity of nitric oxide synthase (NOS) system, in this study we investigated the influence of P. gingivalis LPS on the processes of Src activation in rat sublingual gland acinar cells. The LPS-induced enhancement in the activity of inducible (i) iNOS and the impairment in constitutive (c) cNOS were reflected in the suppression in cSrc activity and the extent of its phosphorylation at Tyr416. Further, we show that the countering effect of ghrelin on the LPS-induced changes in cSrc activity and the extent of its phosphorylation was accompanied by a marked reduction in iNOS and the increase in cNOS activation through phosphorylation at Ser1179. Moreover, the effect of ghrelin on cSrc activation was associated with the kinase S-nitrosylation that was susceptible to the blockage by cNOS inhibition. Our findings suggest that P. gingivalis-induced up-regulation in iNOS leads to disturbances in cNOS phosphorylation that exerts the detrimental effect on the processes of cSrc activation through cNOS mediated S-nitrosylation. We also show that the effect of ghrelin on P. gingivalis-induced inflammatory changes are manifested in the enhancement in cSrc activation through S-nitrosylation and the increase in its phosphorylation at Tyr416.
基金Supported by the National Natural Science Foundation of China, No. 30370643
文摘AIM: To investigate the effect of Tetrandrine (Tet) on LPS-induced NF-κB activation and cell injury in pancreatic acinar cells and to explore the mechanism of Tetrandrine preventing LPS-induced acinar cell injury. METHODS: Male rat pancreatic acinar cells were isolated by collagenase digestion, then exposed to LPS (10 mg/L), Tet (50μmol/L, 100μmol/L) or normal media. At different time point (30 min, 1 h, 4 h, 10 h) after treatment with the agents, cell viability was determined by MTT, the product and nuclear translocation of subunit p65 of NF-κB was visualized by immunofluorescence staining and nuclear protein was extracted to perform EMSA which was used to assay the NF-κB binding activity. RESULTS: LPS induced cell damage directly in a time dependent manner and Tet attenuated LPS-induced cell damage (50μmol/L, P < 0.05; 100μmol/L, P < 0.01). NF-κB p65 immunofluorescence staining in cytoplasm increased and began showing its nuclear translocation within 30 min and the peak was shown at 1 h of LPS 10 mg/L treatment. NF-κB DNA binding activity showed the same alteration pattern as p65 immunofluorescence staining. In Tet group, the immunofluorescence staining in cytoplasm and nuclear translocation of NF-κB were inhibited significantly. CONCLUSION: NF-κB activation is an important early event that may contribute to inflammatory responses and cell injury in pancreatic acinar cells. Tet possesses the protective effect on LPS-induced acinar cell injury by inhibiting NF-κB activation.
文摘BACKGROUND:Acinar cell carcinoma (ACC) is a rare malignancy of the pancreas arising from acinar cells.Unlike ductal adenocarcinoma,this tumor rarely presents with pancreatitis.METHODS:We present a case of ACC associated with chronic calcifying pancreatitis,and a review of the literature focusing on diagnosis and management.RESULTS:A 43-year-old man was proposed for Wirsungojejunal derivation for chronic pancreatitis.Histopathological examination of the tissue extracted revealed an ACC.Duodenopancreatectomy was performed.Six months postoperatively,the patient developed hepatic metastasis and was treated with gemcitabine as palliative chemotherapy.CONCLUSIONS:The clinical presentation of ACC of the pancreas is not specific and the tumor can be underdiagnosed when associated with chronic pancreatitis.Data regarding course,treatment,and prognosis of this tumor are generally lacking.
基金This study was supported by grants from the National Nat-ural Science Foundation of China(81260087 and 81560111)Guangxi Natural Science Foundation(2017GXNSFAA198068).
文摘Background: Previous studies have provided conflicting results regarding whether the serum ghrelin concentration can reflect the severity of acute pancreatitis(AP). The present study examined the correlation between the serum ghrelin concentration and AP severity in animal models and investigated whether altered ghrelin expression in pancreatic acinar cells influences IKK β/NF-κ B signaling and pro-inflammatory cytokine production. Methods: Mild or severe AP was induced in rats by intraperitoneal injection of cerulein or retrograde cholangiopancreatic duct injection of sodium taurocholate, respectively. After successful model induction, serum ghrelin, tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) concentrations were determined by enzyme-linked immunosorbent assay, and IKK β/NF-κ B activation was assessed by immunohistochemistry. Subsequently, stable overexpression or knockdown of ghrelin in AR42 J cells was achieved by lentiviral transfection. After transfected cells and control cells were treated with cerulein for 24 h, the TNF-αand IL-1 β levels in the supernatants were determined by enzyme-linked immunosorbent assay, and the expression levels of p-p65, IKK β, and p-IKK β were detected by Western blotting. Results: In rat AP models, AP severity was correlated with increased IKK β/NF-κ B activation, proinflammatory cytokine production, and ghrelin secretion. The levels of pro-inflammatory cytokines TNF-αand IL-1 β as well as IKK β/NF-κ B signaling activity were increased upon knockdown of ghrelin in the AP acinar cell model and decreased with ghrelin overexpression. Conclusions: Serum ghrelin is related to the severity of AP. Ghrelin may play a protective role in the pathogenesis of AP by inhibiting the pro-inflammatory cytokines and the activation of the IKK β/NF-κ B signaling pathway.
文摘Cell proliferation is an important process in life for growth of normal and cancer cells. The signal transduction pathways activated during this process are strictly regulated. This editorial focuses on the role of nicotine, a mitogen, in the induction of signaling pathways resulting in proliferation of pancreatic tumor cells and compares these events with those in normal acinar cells isolated from the rat pancreas. The data shows striking similarities between these two cellular systems. In addition, the editorial reviews very recent literature of the contribution of MAPK signaling in cell lines associated with human diseases. A prospective cellular model of nicotine induced activation of MAPK cascade is presented.
