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This study was aimed at the preparation and evaluation of walnut meal derived elastase inhibitory peptide (FFVPF) loaded in chitosan-tripolyphosphate (CS-TPP) nanoparticles (NPs). It was shown that the maximum encapsulation efficiency of FFVPF could reach 94.58 ± 0.23%. TEM microphotographs, polydispersity index and zeta-sizer reports indicated that FFVPF-loaded CS-TPP NPs were in nanometric range and were spherical, discrete and uniform in size with PDI less than 0.3. FTIR analysis indicated that the peptides interacted with CS-TPP NPs through strong hydrogen bonds and electrostatic interactions. And the CS-TPP FFVPF NPs showed better stability with heating treatment, pH treatment, or photochemical treatment. Moreover, the in vitro release profile of peptides was identified. The release rate of encapsulated FFVPF was released explosively to 77.22 ± 2.21% and gradually slowed down. These findings highlighted the prospect of CS-TPP NPs as an oral delivery system, and the application of peptides within food and pharmaceutical products.

The aim of this study was to identify the function of the Mg2+ transporter protein solute carrier family 41 member 1 SLC41A1 in pancreatic ductal adenocarcinoma and the underlying mechanisms. A total of 27 solute carrier proteins were differentially expressed in pancreatic ductal adenocarcinoma. Three of these proteins were correlated with clinical outcomes in patients, among which SLC41A1 was downregulated in tumour. Overexpression of SLC41A1 suppressed orthotopic tumour growth in a mouse model and reduced the cell proliferation, colony formation, and invasiveness of KP3 and Panc-1 cells, which may have been associated with the increased population of apoptotic-prone cells. Overexpression of SLC41A1 reduced the mitochondrial membrane potential, induced Bax while suppressed Bcl-2 expression. Suppression of Bax abrogated the tumour-suppressive effects of SLC41A1. Furthermore, overexpression of SLC41A1 promoted Mg2+ efflux and suppressed Akt/mTOR activity, which is the upstream regulator of Bax and Bcl-2. An increase in Akt activity and supplementation with Mg2+ abolished SLC41A1-induced tumour suppression. The results of this study suggest that SLC41A1 may be a potential target for the treatment of pancreatic ductal adenocarcinoma.

Introduction: Primary yolk sac tumor (YST) is an infrequently-diagnosed malignant extragonadal germ cell tumors. It is likely to recur locally and may present with widespread metastases once diagnosed. Primary YST of the head is uncommon but can cause severe complications, such as loss of vision once the tumor mass invades the optic nerve. Patient concerns: A 20-month-old boy presented to the general clinic of the local children's hospital with a complaint of swelling of left face for 1 year and proptosis of the left eye for over 2 weeks as stated by his parents. Initially, he did have some vision, as he could walk by himself, but a special ophthalmologic examination was not performed. Diagnoses: Cranial computed tomography and magnetic resonance imaging revealed a large tumor accompanied by peripheral bone destruction in the left pterygopalatine fossa that extended to sphenoid, ethmoid, left maxillary sinuses, left nasoethmoid, and left orbit. The optic nerve was invaded on both sides. Chest and abdominal imaging were normal. A primary diagnosis of Langerhans cell hyperplasia was made. However, blood tests on the second day of hospitalization revealed significantly elevated serum alpha-fetoprotein levels. On the third day, the boy lost his eyesight, with loss of pupillary and no light sensation during flashlight stimulation on both sides. Interventions: Nasal endoscopy was performed on the fourth day, the vast majority of soft tissue mass was resected for biopsy. Histopathological examination revealed features of endodermal sinus tumor. A final diagnosis of primary YST of pterygopalatine fossa was made. Because the mass could not be resected completely, he received combined chemotherapy with bleomycin, etoposide, and carboplatin for 6 cycles over six months. Outcomes: The patient recovered with significant tumor shrinkage and without secondary metastasis after 18 months but left permanently blind. Conclusion: The worst complication of loss of vision after Primary YST of pterygopalatine fossa alerts us that close physical examination during the initial investigation should be performed, which is especially important in young children who cannot express complaints well. Early detection and treatment with surgical resection and chemotherapy may contribute to satisfactory outcomes and avoidance of visual impairment.

Ideal concentrations of inhaled oxygen with regard to lung protection during early traumatic hemorrhagic shock (THS) remain unknown especially in the era of targeted temperature management (TTM). We speculated that a significant increase in oxygen supply in early stage of THS would magnify the protecting role of hypothermia in acute lung injury. Forty male New Zealand rabbits were randomly divided into four groups (n = 10): sham group, control group, group 1, and group 2. Except for sham group, all other animals were submitted to 30 min of uncontrolled THS and received limited fluid resuscitation for 60 min. During resuscitation, in addition to 34°C of TTM, animals in group 1 inhaled 21% oxygen while animals in group 2 inhaled 50% oxygen. Animals in control group inhaled room air and were kept normothermia. Oxidative stress, inflammation, and apoptosis parameters in the lung tissues were determined. THS induced higher expression of malondialdehyde, surfactant protein A, nuclear factor kappa B, and caspase 3 as well as lower expression of Bcl-2 mRNA and superoxide dismutase activity. Compared with inhalation of 21% oxygen, inhalation of 50% oxygen during TTM significantly improves oxidative stress, inflammation, apoptosis, and acute lung injury. Oxygen supplement during TTM therapy alleviated acute lung injury in the early stage of THS. Further studies are required to explore the ideal combination forms of TTM and oxygen supplement with the purpose of maximizing therapeutic effect while minimizing adverse effects.

Trauma remains a tremendous medical burden partly because of increased expenditure for the management of multiple organ dysfunction syndrome (MODS) developed during hospital stay. The intestinal barrier injury continues to be a second insult resulting in MODS which currently lacks efficient strategies for prevention. Recent studies have uncovered multi-organ protective benefits of atrial natriuretic peptide (ANP) in cardiovascular disease. However, the role of ANP in the prevention of MODS following severe trauma has not been understood. In our laboratory study, 1-h infusion of exogenous ANP during hemorrhagic shock following severe trauma induced high-level expression of endogenous serum ANP after 24 h, this effect was related to the improved level of functional biomarkers in multiple organs. Such phenomenon has not been found in other laboratories. A thorough literature review consequently was performed to uncover the potential mechanisms, to appraise therapy safety, and to propose uncertainties. In severe trauma, short-term exogenous ANP therapy during hemorrhagic shock may promote sustained endogenous expression of ANP from intestinal epithelium through activating a positive feedback loop mechanism involving phospholipase C-γ1 and reactive oxygen species crosstalk. This feedback loop may prevent MODS through multiple signaling pathways. Administration of ANP during hemorrhagic shock is thought to be safe. Further studies are required to confirm our proposed mechanisms and to investigate the dose, duration, and timing of ANP therapy in severe trauma.

Our previous study demonstrated that inhibition of erythropoietin-producing hepatoma cell line-B2 (EphB2) expression resulted in the promotion of cancer growth, with EphB2 acting as a tumor suppressor in pancreatic cancer. Qingyihuaji formula (QYHJ), a traditional Chinese medicine, acts as an independent protective factor for pancreatic cancer patient survival and different patients have shown various responses to QYHJ treatment. In the current study, the different effects on tumor growth inhibition following QYHJ treatment in cells with different levels of EphB2 expression were investi- gated to reveal the mechanism. A subcutaneously transplanted tumor model using cancer cells with different levels of EphB2 expression were established in vivo and received a four-week QYHJ intervention. Tumor weight inhibitory rate and tumor volume deflation were evaluated. The cell cycle and apoptosis were analyzed by flow cytometry, and reverse transcription polymerase chain reaction and western blot analysis were used to assess mRNA and protein levels. The results showed that the tumor weight inhibitory rate was 31.40, 31.33 and 18.36% in CFPAC-1, CFPAC-1 control RNAi and CFPAC-1 EphB2 RNAi cells following QYHJ treatment, respectively. A statistically significant difference was identified in CFPAC‑1 (P

We read with great interest the article by Tarvasmaki et al. [1], who observed the relationship between vasopressor/inotrope use and outcome in patients with cardiac shock (CS). Their results indicate that use of adrenaline in CS is associated with increased 90-day mortality and marked worsening of cardiac and renal biomarkers during the first few days. The study underscores the need for randomized controlled trials of adrenaline versus noradrenaline in CS.

Background. Qingyihuaji formula (QYHJ) is a widely used herbal formula that has shown promising antitumor effect in the treatment of pancreatic cancer in the Cancer Hospital, Fudan University, Shanghai, China. Objective. This research was conducted to study whether Ski acts as a therapeutic target of QYHJ formula in the treatment of SW1990 pancreatic cancer. Methods. The expression changes of Ski mRNA and protein in SW1990 pancreatic cancer subcutaneously transplanted tumor treated with QYHJ were detected by real-time polymerase chain reaction and Western blot. Then, we established a stable transfection SW1990 cell with low expression of Ski through lentivirus-mediated RNA interference (RNAi) technique. The responses to QYHJ treatment on a subcutaneously transplanted tumor with different Ski expression statuses were evaluated. Finally, the effect of Ski downregulation on SW1990 cell biological behavior was also evaluated. Results. Expression of Ski mRNA and protein in SW1990 subcutaneously transplanted tumor decreased dramatically after the treatment with QYHJ. Stable transfection cells with low expression of Ski (SW1990/Ski RNAi) were created, and negative vector-transfected cells (SW1990/con RNAi) were used as controls. The tumor weight inhibitory rates of QYHJ on subcutaneously transplanted tumors formed by SW1990 or SW1990/con RNAi were 29.6% and 32.2%, respectively, whereas they were 16.0% to 17.8% when the tumors were formed by SW1990/Ski RNAi. Ski downregulation sensitized the response of SW1990 cells to TGF-β1-induced growth inhibition in vitro. Flow cytometric analyses revealed that the percentage of cells in the G1 phase increased from 40.4% to 62.9% when Ski was downregulated. The subcutaneously transplanted tumors formed by SW1990/Ski RNAi grew much more slowly than those formed by parental and control vector—transfected cells. Conclusion. Ski acts as therapeutic target of QYHJ in the treatment of SW1990 pancreatic cancer cells, and its expression status mediates different responses to QYHJ treatment.

Ski used to be defined as an oncogene that contributes to the resistance of tumor cells to transforming growth factor-beta (TGF-beta)-induced growth arrest. As TGF-beta has a dual effect on tumor growth with both tumor-suppressing and -promoting activity depending on the stage of carcinogenesis and the cell type, the precise role of Ski in carcinogenesis remains unclear. In this study, we show that downregulation of Ski through lentivirus-mediated RNA interference decreases tumor growth both in vitro and in vivo, yet promotes cell invasiveness in vitro, and lung metastasis in vivo in the pancreatic cancer cell line SW1990, which contain wild-type Smad4 expression, and the BxPC3 cell line, which is Smad4 deficient. We also show that the downregulation of Ski increases TGF-beta-induced transcriptional activity, which is associated with increased TGF-beta-dependent Smad2/3 phosphorylation, and results in an altered expression profile of TGF-beta-inducible genes involved in metastasis, angiogenesis and cell proliferation and epithelial-mesenchymal transition. Immunohistochemical analysis of specimens from 71 patients with pancreatic adenocarcinoma showed a significant association between overexpression of Ski and decreased patient survival time (P = 0.0024). Our results suggest that Ski may act as a tumor proliferation-promoting factor or as a metastatic suppressor in human pancreatic cancer.