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| 2. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Chen, Ke-Ling, et al.
(författare)
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Effects of Tocilizumab on Experimental Severe Acute Pancreatitis and Associated Acute Lung Injury
- 2016
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Ingår i: Critical Care Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0090-3493 .- 1530-0293. ; 44:8, s. E664-E677
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the therapeutic effects of tocilizumab, an antibody against interleukin-6 receptor, on experimental severe acute pancreatitis and associated acute lung injury. The optimal dose of tocilizumab and the activation of interleukin-6 inflammatory signaling were also investigated. Design: Randomized experiment. Setting: Research laboratory at a university hospital. Subject: Experimental severe acute pancreatitis in rats. Interventions: Severe acute pancreatitis was induced by retrograde injection of sodium taurocholate (50 mg/kg) into the biliopancreatic duct. In dose-study, rats were administered with different doses of tocilizumab (1, 2, 4, 8, and 16 mg/kg) through the tail vein after severe acute pancreatitis induction. In safety-study, rats without severe acute pancreatitis induction were treated with high doses of tocilizumab (8, 16, 32, and 64 mg/kg). Serum and tissue samples of rats in time-study were collected for biomolecular and histologic evaluations at different time points (2, 6, 12, 18, and 24 hr). Measurements and Main Results: 1) Under the administration of tocilizumab, histopathological scores of pancreas and lung were decreased, and severity parameters related to severe acute pancreatitis and associated lung injury, including serum amylase, C-reactive protein, lung surfactant protein level, and myeloperoxidase activity, were all significant alleviated in rat models. 2) Dose-study demonstrated that 2 mg/kg tocilizumab was the optimal treatment dose. 3) Basing on multi-organ pathologic evaluation, physiological and biochemical data, no adverse effect and toxicity of tocilizumab were observed in safety-study. 4) Pancreatic nuclear factor-kappa B and signal transducer and activator of transcription 3 were deactivated, and the serum chemokine (C-X-C motif) ligand 1 was down-regulated after tocilizumab administration. Conclusions: Our study demonstrated tocilizumab, as a marketed drug commonly used for immune-mediated diseases, was safe and effective for the treatment of experimental severe acute pancreatitis and associated acute lung injury. Our findings provide experimental evidences for potential clinical application of tocilizumab in severe acute pancreatitis and associated complications.
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| 4. |
- Liu, Yong, et al.
(författare)
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Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-kappa B activity
- 2017
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Ingår i: Cell Death and Disease. - : NATURE PUBLISHING GROUP. - 2041-4889. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of L-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor kappa B (NF-kappa B) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-kappa B activation and less release of TNF-alpha and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that inhibition of XIAP represents a potential therapeutic strategy for the treatment of acute pancreatitis.
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| 5. |
- Liu, Yong, et al.
(författare)
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Resolvin D1 protects against inflammation in experimental acute pancreatitis and associated lung injury
- 2016
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Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : AMER PHYSIOLOGICAL SOC. - 0193-1857 .- 1522-1547. ; 310:5, s. G303-G309
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Tidskriftsartikel (refereegranskat)abstract
- Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure with considerable mortality. Recently, resolvin D1 (RvD1) as an endogenous anti-inflammatory lipid mediator has been confirmed to protect against many inflammatory diseases. This study was designed to investigate the effects of RvD1 in acute pancreatitis and associated lung injury. Acute pancreatitis varying from mild to severe was induced by cerulein or cerulein combined with LPS, respectively. Mice were pretreated with RvD1 at a dose of 300 ng/mouse 30 min before the first injection of cerulein. Severity of AP was assessed by biochemical markers and histology. Serum cytokines and myeloperoxidase (MPO) levels in pancreas and lung were determined for assessing the extent of inflammatory response. NF-kappa B activation was determined by Western blotting. The injection of cerulein or cerulein combined with LPS resulted in local injury in the pancreas and corresponding systemic inflammatory changes with pronounced severity in the cerulein and LPS group. Pretreated RvD1 significantly reduced the degree of amylase, lipase, TNF-alpha, and IL-6 serum levels; the MPO activities in the pancreas and the lungs; the pancreatic NF-kappa B activation; and the severity of pancreatic injury and associated lung injury, especially in the severe acute pancreatitis model. These results suggest that RvD1 is capable of improving injury of pancreas and lung and exerting anti-inflammatory effects through the inhibition of NF-kappa B activation in experimental acute pancreatitis, with more notable protective effect in severe acute pancreatitis. These findings indicate that RvD1 may constitute a novel therapeutic strategy in the management of severe acute pancreatitis.
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| 6. |
- Sun, Hui-Min, et al.
(författare)
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SERPINA4 is a novel independent prognostic indicator and a potential therapeutic target for colorectal cancer
- 2016
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Ingår i: American Journal of Cancer Research. - Madison : E-CENTURY PUBLISHING CORP. - 2156-6976. ; 6:8, s. 1636-1649
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Tidskriftsartikel (refereegranskat)abstract
- Serpina family A member 4 (SERPINA4), also known as kallistatin, exerts important effects in inhibiting tumor growth and angiogenesis in many malignancies. However, the precise role of SERPINA4 in CRC has not been fully elucidated. The present study aimed to investigate the expression of SERPINA4 and its clinical significance in CRC. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses showed that the mRNA and protein expression of SERPINA4 in colorectal cancer (CRC) specimens was significantly decreased than that in adjacent normal mucosa. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of SERPINA4 by using a tissue microarray (TMA) containing 327 archived paraffin-embedded CRC specimens. Statistical analyses revealed that decreased SERPINA4 expression was significantly associated with invasion depth, nodal involvement, distant metastasis, American Joint Committee on Cancer (AJCC) stage, and tumor differentiation. SERPINA4 was also an independent prognostic indicator of disease-free survival and overall survival in patients with CRC. Furthermore, the impact of altered SERPINA4 expression on CRC cells was analyzed with a series of in vitro and in vivo assays. The results demonstrated that SERPINA4 significantly inhibits malignant tumor progression and serves as a novel prognostic indicator and a potential therapeutic target for CRC.
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| 7. |
- Yang, Lie, et al.
(författare)
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Efficacy of Surgery and Adjuvant Therapy in Older Patients With Colorectal Cancer A STROBE-compliant article
- 2014
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Ingår i: Medicine. - : Lippincott, Williams andamp; Wilkins. - 0025-7974 .- 1536-5964. ; 93:28
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Tidskriftsartikel (refereegranskat)abstract
- The present study aimed to assess the efficacy of surgery and adjuvant therapy in older patients (age greater than= 70 years) with colorectal cancer (CRC). Older CRC patients are under-represented in available clinical trials, and therefore their outcomes after receiving surgery and adjuvant therapy are unclear. From two prospective Swedish databases, we assessed a cohort of 1021 patients who underwent curative surgery for stage I, II, or III primary CRC, with or without adjuvant chemotherapy/ radiotherapy. Of the patients with colon cancer (n = 467), 182 (39%) were aged less than70 years, 162 (35%) aged 70 to 80 years, and 123 (26%) were aged greater than= 80 years. Of rectal cancer patients (n = 554), 264 (48%) were aged less than70 years, 234 (42%) aged 70 to 80 years, and 56 (10%) aged greater than= 80 years. Older patients with either colon or rectal cancer had higher comorbidity than did younger patients. Older patients with colon cancer had equivalent postoperative morbidity and 30-day mortality to younger patients. Rectal cancer patients aged greater than= 80 years had a higher 30-day mortality than younger patients (odds ratio OR], 2.37; 95% confidence interval CI], 1.6-4.55; P = 0.03). For either colon or rectal cancer, adjuvant chemotherapy compromised the 5-year overall survival (OS) of older patients with stage II disease and had no effect on those with stage III disease. Receiving adjuvant chemotherapy was a poor factor of OS for older patients with either colon (HR 1.88, 95% CI: 1.20-4.35, P = 0.03) or rectal cancer (HR 1.72, 95% CI: 1.052.26, P = 0.004). Preoperative short-course radiotherapy improved both OS and local control for older patients with stage III rectal cancer and had no effect on those with stage II disease. Radiotherapy was a favorable factor for the OS of the older patients with rectal cancer (HR 0.42, 95% CI: 0.21-3.57, P = 0.01). In conclusion, Older CRC patients had equal safety of surgery as younger patients, except rectal cancer patients aged greater than= 80 years that had a higher mortality. Adjuvant 5FU-based chemotherapy did not benefit older CRC patient, while neoadjuvant radiotherapy improved the prognosis of older patients with stage III rectal cancer.
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| 8. |
- Zhao, Shi-Wei, et al.
(författare)
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Haplotype-resolved genome assembly of Coriaria nepalensis a non-legume nitrogen-fixing shrub
- 2023
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Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Coriaria nepalensis Wall. (Coriariaceae) is a nitrogen-fixing shrub which forms root nodules with the actinomycete Frankia. Oils and extracts of C. nepalensis have been reported to be bacteriostatic and insecticidal, and C. nepalensis bark provides a valuable tannin resource. Here, by combining PacBio HiFi sequencing and Hi-C scaffolding techniques, we generated a haplotype-resolved chromosome-scale genome assembly for C. nepalensis. This genome assembly is approximately 620 Mb in size with a contig N50 of 11 Mb, with 99.9% of the total assembled sequences anchored to 40 pseudochromosomes. We predicted 60,862 protein-coding genes of which 99.5% were annotated from databases. We further identified 939 tRNAs, 7,297 rRNAs, and 982 ncRNAs. The chromosome-scale genome of C. nepalensis is expected to be a significant resource for understanding the genetic basis of root nodulation with Frankia, toxicity, and tannin biosynthesis.
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