PURPOSE: This study aimed to elucidate the molecular mechanisms of the anti-pancreatic fibrosis effects of matrine in rats. MATERIALS AND METHODS: Trinitrobenzene sulfonic acid was administrated to rats to establish a pancreatic fibrosis model. Rats were divided into four groups: Control, Sham, Model, and Matrine (n=8). Hematoxylin-eosin staining, Masson staining, and Azan staining were performed to evaluate pancreatic fibrosis. Expression of transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA), and collagen I in pancreatic tissues was evaluated by immunohistochemical staining. mRNA and protein levels of TGF-β receptor 1 (TβR1), TβR2, and Smad2 in pancreatic tissues were determined by RT-PCR and Western blot, respectively. RESULTS: In the model group, hyperplasia of glandules around the glandular ducts, mitochondrial swelling of acinous cells, and severe fibrosis were found. Interestingly, in the Matrine group, mitochondrial swelling was only found in a small number of acinous cells, and the fundamental structures of pancreatic tissues were intact. Moreover, pancreatic fibrosis was markedly alleviated. Comparing to the Sham group, expression of α-SMA, TGF-β1, and collagen I was sharply elevated in the Model group (p < 0.05); however, their expressions were much lower in the Matrine group, compared to the Model group (p < 0.05). Compared with the Sham group, mRNA and protein levels of Smad2, TβR1, and TβR2 in the Model group were notably raised (p < 0.05). However, their high expression was significantly downregulated in the Matrine group (p < 0.05). CONCLUSION: Matrine suppressed pancreatic fibrosis by regulating TGF-β/Smad signaling in rats.
Acinar Cells ; Actins ; Animals ; Blotting, Western ; Collagen ; Fibrosis* ; Hyperplasia ; Mitochondrial Swelling ; Rats* ; RNA, Messenger ; Signal Transduction

Corticosteroids are used in the treatment of many diseases; however, they also induce various side effects. Dexamethasone is one of the most potent corticosteroids, and it has been reported to induce the side effect of impaired salivary gland function. This study aimed to evaluate the effects of dexamethasone on mouse submandibular gland function to gain insight into the mechanism of dexamethasone-induced salivary hypofunction. The muscarinic agonist carbachol (CCh) induced salivary secretion and was not affected by short-term dexamethasone treatment but was decreased following long-term dexamethasone administration. The expression levels of the membrane proteins Na-K-2Cl cotransporter, transmembrane member 16A, and aquaporin 5 were comparable between the control and long-term dexamethasone treatment groups. The CCh-induced increase in calcium concentration was significantly lower in the presence of extracellular Ca in the long-term dexamethasone treatment group compared to that in the control group. Furthermore, CCh-induced salivation in the absence of extracellular Ca and Ca ionophore A23187-induced salivation was comparable between the control and long-term dexamethasone treatment groups. Moreover, salivation induced by the Ca-ATPase inhibitor thapsigargin was diminished in the long-term dexamethasone treatment group. In summary, these results demonstrate that short-term dexamethasone treatment did not impair salivary gland function, whereas long-term dexamethasone treatment diminished store-operated Ca entry, resulting in hyposalivation in mouse submandibular glands.
Acinar Cells ; drug effects ; metabolism ; Animals ; Calcium ; metabolism ; Calcium Signaling ; drug effects ; Carbachol ; pharmacology ; Dexamethasone ; therapeutic use ; Mice ; Muscarinic Agonists ; pharmacology ; Saliva ; metabolism ; Salivation ; drug effects ; Submandibular Gland ; drug effects ; metabolism

Sjögren's syndrome (SS) is a chronic heterogeneous disease that mainly affects exocrine glands, leading to sicca syndromes such as xerostomia. Despite the second highest prevalence rate among systemic autoimmune diseases, its pathophysiology remains largely unknown. Here we report that SKG mice, a cardinal model of Th17 cell-mediated arthritis, also develop a secondary form of SS-like disorder upon systemic exposure to purified curdlan, a type of β-glucan. The reduced production of saliva was not caused by focal immune cell infiltrates but was associated with IgG deposits in salivary glands. Sera from curdlan-injected SKG mice contained elevated titers of IgG (predominantly IgG1), autoantibody to the muscarinic type 3 receptor (M3R) and inhibited carbachol-induced Ca2+ signaling in salivary acinar cells. These results suggest that the Th17 cells that are elicited in SKG mice promote the production of salivary gland-specific autoantibodies including anti-M3R IgG; the antibodies are then deposited on acinar cells and inhibit M3R-mediated signaling required for salivation, finally leading to hypofunction of the salivary glands. This type II hypersensitivity reaction may explain the origin of secondary SS occurring without focal leukocyte infiltrates.
Acinar Cells ; Animals ; Antibodies ; Arthritis ; Autoantibodies ; Autoimmune Diseases ; Exocrine Glands ; Hypersensitivity ; Immunoglobulin G ; Leukocytes ; Mice ; Prevalence ; Saliva ; Salivary Glands ; Salivation ; Sjogren's Syndrome ; Th17 Cells ; Xerostomia

BACKGROUND: Chronic pancreatitis (CP) is an irreversible progressive disease that destroys exocrine parenchyma, which are replaced by fibrous tissue. As pancreatic fibrosis is a key feature of CP, reducing fibrotic protein content in the pancreas is crucial for preventing CP. Studies suggest that NF-κB facilitates the expression of fibrotic mediators in pancreas and protein kinase C-δ (PKC-δ) regulates NF-κB activation in stimulated pancreatic acinar cells. Docosahexaenoic acid (DHA) is an omega-3 fatty acid having anti-inflammatory and anti-fibrotic effects. It has been shown to inhibit NF-κB activity in cerulein-stimulated pancreatic acinar cells which is a cellular model of CP. In the present study, we investigated if DHA inhibits expression of fibrotic mediators by reducing PKC-δ and NF-κB expression in mouse pancreatic tissues with CP.METHODS: For six weeks, mice were weekly induced for acute pancreatitis to develop CP. Furthermore, acute pancreatitis was induced by hourly intraperitoneal injections of cerulein (50 μg/kg × 7). Mice were administered DHA (10 μM) via drinking water before and after CP induction.RESULTS: Cerulein-induced pancreatic damages like decreased pancreatic weight/total body weight, leukocyte infiltration, necrosis of acinar cells, and vacuolization were found to be inhibited by DHA. Additionally, DHA inhibited cerulein-induced fibrotic mediators like alpha-smooth muscle actin and fibronectin in pancreas. DHA reduced expression of PKC-δ and NF-κB p65 in pancreatic tissues of cerulein-treated mice.CONCLUSIONS: DHA may be beneficial in preventing CP by suppressing pancreatic expression of fibrotic mediators.
Acinar Cells ; Actins ; Animals ; Body Weight ; Ceruletide ; Drinking Water ; Fibronectins ; Fibrosis ; Injections, Intraperitoneal ; Leukocytes ; Mice ; Necrosis ; Pancreas ; Pancreatitis ; Pancreatitis, Chronic ; Protein Kinases

Serine protease inhibitor Kazal-type 1 (SPINK1) is a gene expressed from pancreatic acinar cell which its mutation is known to be associated with chronic pancreatitis (CP) and pancreatic cancer. We report a case of a 47-years-old female with nausea and weight loss with yellow discoloration of skin. Initial imaging and endoscopic study led us to an impression of chronic pancreatitis with pancreatic cancer with common bile-duct dilation. Biopsy result was confirmed with pancreatic adenocarcinoma and additional imaging revealed lymph node and bone metastasis. Our genetic analysis revealed 194+2T>C mutation of SPINK1. Biliary obstruction was successfully decompressed by stent insertion and underwent chemotherapy and radiotherapy. Although there is accumulating evidence of association between SPINK1 mutation and CP, the relationship between SPINK1 mutation and pancreatic cancer in CP patient is an emerging concept. Genetic analysis should be considered in patients with young age especially when diagnosed with both CP and pancreatic cancer.
Acinar Cells ; Adenocarcinoma ; Biopsy ; Drug Therapy ; Female ; Genes, vif ; Humans ; Jaundice, Obstructive ; Lymph Nodes ; Nausea ; Neoplasm Metastasis ; Pancreatic Neoplasms ; Pancreatitis, Chronic ; Radiotherapy ; Serine Proteases ; Skin ; Stents ; Weight Loss

OBJECTIVETo investigated the anti-inflammatory and antimicrobial effects of anthocyanins extracted from black soybean on the chronic bacterial prostatitis (CBP) rat model.

METHODSThe Sprague-Dawley rats were divided into 4 groups, including control, ciprofloxacin, anthocyanins and anthocyanins with ciprofloxacin groups (n=8 in each group). Then, drip infusion of bacterial suspension (Escherichia coli Z17 O:K:H) into Sprague-Dawley rats was conducted to induce CBP. In 4 weeks, results of prostate tissue, urine culture, and histological analysis on the prostate were analyzed for each group.

RESULTSThe use of ciprofloxacin, anthocyanins, and anthocyanins with ciprofloxacin showed statistically significant decreases in bacterial growth and improvements in the reduction of prostatic inflammation compared with the control group (P<0.05). The anthocyanins with ciprofloxacin group showed a statistically significant decrease in bacterial growth and improvement in prostatic inflammation compared with the ciprofloxacin group (P<0.05).

CONCLUSIONSThese results suggest that anthocyanins may have anti-inflammatory and antimicrobial effects, as well as a synergistic effect with ciprofloxacin. Therefore, we suggest that the combination of anthocyanins and ciprofloxacin may be effective in treating CBP to obtain a higher rate of treatment success.

Acinar Cells ; drug effects ; pathology ; Animals ; Anthocyanins ; isolation & purification ; pharmacology ; therapeutic use ; Anti-Infective Agents ; pharmacology ; therapeutic use ; Anti-Inflammatory Agents ; pharmacology ; therapeutic use ; Chronic Disease ; Disease Models, Animal ; Escherichia coli Infections ; drug therapy ; urine ; Fibrosis ; Inflammation ; pathology ; Male ; Plant Extracts ; pharmacology ; therapeutic use ; Prostate ; drug effects ; microbiology ; pathology ; Prostatitis ; drug therapy ; microbiology ; urine ; Rats, Sprague-Dawley ; Severity of Illness Index ; Soybeans ; chemistry ; Urine ; microbiology

PURPOSE: Postoperative pancreatic fistula is a serious and fatal complication of gastrectomy for gastric cancer. Blunt trauma to the parenchyma of the pancreas can result from an assistant's forceps compressing and retracting the pancreas, which in turn may result in pancreatic juice leakage. However, no published studies have focused on blunt trauma to the pancreas during laparoscopic surgery. Our aim was to investigate the relationship between compression of the pancreas and pancreatic juice leakage in a swine model. MATERIALS AND METHODS: Three female pigs were used in this study. The pancreas was gently compressed dorsally for 15 minutes laparoscopically with gauze grasped with forceps. Pancreatic juice leakage was visualized by fluorescence imaging after topical administration of chymotrypsin-activatable fluorophore in real time. Amylase concentrations in ascites collected at specified times was measured. In addition, pancreatic tissue was fixed with formalin, and the histology of the compressed sites was evaluated. RESULTS: Fluorescence imaging enabled visualization of pancreatic juice leaking into ascites around the pancreas. Median concentrations of pancreatic amylase in ascites increased from 46 U/L preoperatively to 12,509 U/L 4 hours after compression. Histological examination of tissues obtained 4 hours after compression revealed necrotic pancreatic acinar cells extending from the surface to deep within the pancreas and infiltration of inflammatory cells. CONCLUSIONS: Pancreatic compression by the assistant's forceps can contribute to pancreatic juice leakage. These findings will help to improve the procedure for lymph node dissection around the pancreas during laparoscopic gastrectomy.
Acinar Cells ; Administration, Topical ; Amylases ; Ascites ; Female ; Formaldehyde ; Gastrectomy* ; Hand Strength ; Humans ; Laparoscopy ; Lymph Node Excision* ; Lymph Nodes* ; Optical Imaging ; Pancreas ; Pancreatic Fistula ; Pancreatic Juice ; Stomach Neoplasms ; Surgical Instruments ; Swine ; Wounds, Nonpenetrating

Recent findings indicate that Type 2 taste receptors (T2Rs) are expressed outside the gustatory system, including in the gastrointestinal tracts and the exocrine glands, such as the submandibular (SM), parotid (P), lacrimal (L) glands and pancreas (PC). Specifically, T2Rs are found in some of the gastrointestinal endocrine cells, and these cells secreted peptide hormones in response to stimulation by bitter-tasting compounds. The results show that T2Rs may have significant physiological roles besides bitter taste reception. The functions of the T2Rs in the exocrine glands remain poorly understood. An expression levels analysis of T2Rs will help to determine those functions in the exocrine glands. The expression levels of the T2Rs in the exocrine glands were discovered via the qPCR. C57BL/6J mice of 42~60-day-old were used. Messenger RNAs were extracted from S, P, L and PC. Cloned DNAs were synthesized by reverse transcription. Quantitative PCRs were performed using the SYBR Green method. The expression levels of the T2Rs were calculated as relative expression levels to that of the GAPDH. The statistical significance among the observed exocrine glands was tested using the variance analysis (ANOVA test). Tas2r108, out of murine 35 T2Rs, was the most highly expressed in every observed exocrine gland. This finding was similar to previous results from tongue papillae, but the expression levels were lower than those of the tongue papillae. Tas2r137 of SM, P, L and PC were expressed a little lower than that of tongue papillae. The T2Rs in the exocrine glands may play slightly different roles from those in the tongue. We suggest that physiological studies such as a patch clamp and functional Ca²⁺ imaging of acinar cells are necessary for understanding the Tas2r108 functions.
Acinar Cells ; Animals ; Clone Cells ; DNA ; Enteroendocrine Cells ; Exocrine Glands ; Gastrointestinal Tract ; Methods ; Mice ; Pancreas ; Peptide Hormones ; Polymerase Chain Reaction ; Reverse Transcription ; RNA, Messenger ; Tongue

Intracellular Ca²⁺ mobilization is closely linked with the initiation of salivary secretion in parotid acinar cells. Reactive oxygen species (ROS) are known to be related to a variety of oxidative stress-induced cellular disorders and believed to be involved in salivary impairments. In this study, we investigated the underlying mechanism of hydrogen peroxide (H₂O₂) on cytosolic Ca²⁺ accumulation in mouse parotid acinar cells. Intracellular Ca²⁺ levels were slowly elevated when 1 mM H₂O₂ was perfused in the presence of normal extracellular Ca²⁺. In a Ca²⁺-free medium, 1 mM H₂O₂ still enhanced the intracellular Ca²⁺ level. Ca²⁺ entry tested using manganese quenching technique was not affected by perfusion of 1 mM H₂O₂. On the other hand, 10 mM H₂O₂ induced more rapid Ca²⁺ accumulation and facilitated Ca²⁺ entry from extracellular fluid. Ca²⁺ refill into intracellular Ca²⁺ store and inositol 1,4,5-trisphosphate (1 µM)-induced Ca²⁺ release from Ca²⁺ store was not affected by 1 mM H₂O₂ in permeabilized cells. Ca²⁺ efflux through plasma membrane Ca²⁺-ATPase (PMCA) was markedly blocked by 1 mM H₂O₂ in thapsigargin-treated intact acinar cells. Antioxidants, either catalase or dithiothreitol, completely protected H₂O₂-induced Ca²⁺ accumulation through PMCA inactivation. From the above results, we suggest that excessive production of H₂O₂ under pathological conditions may lead to cytosolic Ca²⁺ accumulation and that the primary mechanism of H₂O₂-induced Ca²⁺ accumulation is likely to inhibit Ca²⁺ efflux through PMCA rather than mobilize Ca²⁺ ions from extracellular medium or intracellular stores in mouse parotid acinar cells.
Acinar Cells* ; Animals ; Antioxidants ; Calcium ; Catalase ; Cell Membrane* ; Cytosol ; Dithiothreitol ; Extracellular Fluid ; Hand ; Hydrogen Peroxide* ; Hydrogen* ; Inositol 1,4,5-Trisphosphate ; Ions ; Manganese ; Mice* ; Perfusion ; Plasma Membrane Calcium-Transporting ATPases ; Plasma* ; Reactive Oxygen Species

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.
Acinar Cells/pathology* ; Aged ; Biopsy ; Cell Proliferation ; Digital Rectal Examination ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Predictive Value of Tests ; Prostate/pathology* ; Prostatic Neoplasms/pathology* ; Retrospective Studies ; Testosterone/blood*