Central venous-to-arterial carbon dioxide partial pressure difference as a guiding parameter for cardiotonic drug administration in patients with early-stage septic shock.

OBJECTIVE: This study aimed to investigate the effect of the central venous-to-arterial carbon dioxide partial pressure difference (Pcv-aCO2) on the administration of cardiotonic drugs in patients with early-stage septic shock. METHODS: A retrospective study was conducted on 120 patients suffering from septic shock. At admission, the left ventricular ejection fraction (LVEF) and Pcv-aCO2 of the patients were obtained. On the premise of mean arterial pressure (MAP) ≥ 65 mmHg, the patients were divided into two groups according to the treatment approaches adopted by different doctors-Control group: LVEF ≤50%; Observation group: Pcv-aCO2 ≥ 6. Both groups received cardiotonic therapy. RESULTS: The two groups of patients had similar general conditions and pre-resuscitation conditions ( P > 0.05). Compared to the Control group, the Observation group had a higher MAP, Lac clearance rate, and urine output after six hours of resuscitation ( P < 0.05), but a lower absolute value of Lac, total fluid intake in 24 hours, and a lower number of patients receiving renal replacement therapy during hospitalization ( P < 0.05). After six hours of resuscitation, the percentages of patients meeting central venous oxygen saturation and central venous pressure targets were not significantly different between the Control and Observation groups ( P > 0.05). There was no difference in the 28-day mortality rate between the two groups ( P > 0.05). CONCLUSION: Pcv-aCO2 is more effective than LVEF in guiding the administration of cardiotonic drugs in the treatment of patients with septic shock.

Comparative effects of pectin and hydrolyzed pectin coating as pre-frying treatments on acrylamide formation in potato chips.

This study aimed to compare the effects of pectin and hydrolyzed pectin coating as pre-frying treatments on acrylamide content and quality characteristics of fried potato chips. The hydrolyzed pectin with molecular weight (Mw) of 8.81 ± 0.49 kDa was obtained through partial degradation of pectin (Mw: 747.57 ± 6.73 kDa) using pectinase. Results showed that both pectin and hydrolyzed pectin coating significantly inhibited acrylamide formation and inhibition rates exceeded 90 %. Hydrolyzed pectin had stronger inhibitory activity against acrylamide formation than pectin, especially when the concentration of hydrolyzed pectin was >2 %, its inhibitory rate exceeded 95 %. Compared to pectin coating, hydrolyzed pectin coating endow fried potato chips with smaller browning, higher crispness, less moisture but higher oil content. Overall, hydrolyzed pectin had better application prospects than pectin in inhibiting acrylamide formation of fried potato chips.

A chromosome-level genome assembly for Onobrychis viciifolia reveals gene copy number gain underlying enhanced proanthocyanidin biosynthesis.

Sainfoin (Onobrychis viciifolia), which belongs to subfamily Papilionoideae of Leguminosae, is a vital perennial forage known as "holy hay" due to its high contents of crude proteins and proanthocyanidins (PAs, also called condensed tannins) that have various pharmacological properties in animal feed, such as alleviating rumen tympanic disease in ruminants. In this study, we select an autotetraploid common sainfoin (2n = 4x = 28) and report its high-quality chromosome-level genome assembly with 28 pseudochromosomes and four haplotypes (~1950.14 Mb, contig N50 = 10.91 Mb). The copy numbers of genes involved in PA biosynthesis in sainfoin are significantly greater than those in four selected Fabales species, namely, autotetraploid Medicago sativa and three other diploid species, Lotus japonicus, Medicago truncatula, and Glycine max. Furthermore, gene expansion is confirmed to be the key contributor to the increased expression of these genes and subsequent PA enhancement in sainfoin. Transcriptomic analyses reveal that the expression of genes involved in the PA biosynthesis pathway is significantly increased in the lines with high PA content compared to the lines with medium and low PA content. The sainfoin genome assembly will improve our understanding of leguminous genome evolution and biosynthesis of secondary metabolites in sainfoin.

Current status and future prospects of chimeric antigen receptor-T cell therapy in lymphoma research: A bibliometric analysis.

CAR-T cell therapy, a novel therapeutic approach that has attracted much attention in the field of cancer treatment at present, has become the subject of many studies and has shown great potential in the treatment of hematological malignancies, such as leukemia and lymphoma. This study aims to analyze the characteristics of articles published on CAR-T cell therapy in the lymphoma field and explore the existing hotspots and frontiers. The relevant articles published from 2013 to 2022 were retrieved from the Web of Science Core Collection. CiteSpace, VOSviewer, Bibliometric online analysis platform, Microsoft Excel, and R software were used for bibliometric analysis and visualization. The number of publications related to the research has been increasing year by year, including 1023 articles and 760 reviews from 62 countries and regions, 2092 institutions, 1040 journals, and 8727 authors. The United States, China, and Germany are the main publishing countries in this research field. The top 10 institutions are all from the United States, the journal with the highest impact factor is BLOOD, the author with the most publications is Frederick L Locke, and the most influential author is Carl H June. The top three keywords are "Lymphoma," "Immunotherapy," and "Therapy." "Maude (2014)" is the most cited and strongest burstiness reference over the past decade. This study provides a comprehensive bibliometric analysis of CAR-T cell therapy in lymphoma, which can help researchers understand the current research hotspots in this field, explore potential research directions, and identify future development trends.

Quantitative parameters in novel spectral computed tomography for assessing gastric cancer and cell proliferation.

OBJECTIVES: To investigate the diagnostic ability of novel spectral CT-derived parameters for gastric cancer histological types and Ki-67 expression. METHODS: A total of 72 patients with histologically proven gastric cancer (GC) were retrospectively included in this study. All patients underwent dual-phase enhanced abdominal spectral CT. The arterial (AP) and venous phase (VP) slope of the spectral curve (λHU), iodine concentration (IC), normalized IC (NIC), effective atomic number (Zeff) and iodine-no-water concentration were retrospectively compared between patients with low and high Ki-67 expression levels and with different histological types in GC patients. The ROI was outlined independently by two senior physicians, and the average of three measurements at the largest level was taken. In addition, interobserver reproducibility was assessed by Bland-Altman analysis. Correlations between quantitative parameters and Ki-67 expression levels were assessed by Spearman's correlation coefficients. RESULTS: The values between the mucinous group and nonmucinous carcinoma group were significantly different in both phases. The IC, NIC, and iodine-no-water concentration in the VP were significantly different among the Ki-67_L, Ki-67_M, and Ki-67_H groups. Spearman rank correlation analysis demonstrated a positive correlation between Ki-67 expression levels and IC, NIC, and iodine-no-water concentration in the VP, with correlation coefficients of 0.304, 0.424, and 0.322, respectively. CONCLUSION: Quantitative spectral parameters can discriminate between low and high Ki-67 expression and different histological types in GC. The NIC, IC and iodine-no-water concentration can be useful parameters for evaluating of Ki-67 expression levels.

KIF6 Trp719Arg Genetic Variant Increases Risk for Thoracic Aortic Dissection.

BACKGROUND: KIF6 (kinesin family member 6), a protein coded by the KIF6 gene, serves an important intracellular function to transport organelles along microtubules. In a pilot study, we found that a common KIF6 Trp719Arg variant increased the propensity of thoracic aortic aneurysms (TAA) to suffer dissection (AD). The present study aims for a definite investigation of the predictive ability of KIF6 719Arg vis à vis AD. Confirmatory findings would enhance natural history prediction in TAA. METHODS: 1108 subjects (899 aneurysm and 209 dissection patients) had KIF6 719Arg variant status determined. RESULTS: The 719Arg variant in the KIF6 gene correlated strongly with occurrence of AD. Specifically, KIF6 719Arg positivity (homozygous or heterozygous) was substantially more common in dissectors (69.8%) than non-dissectors (58.5%) (p = 0.003). Odds ratios (OR) for suffering aortic dissection ranged from 1.77 to 1.94 for Arg carriers in various dissection categories. These high OR associations were noted for both ascending and descending aneurysms and for homozygous and heterozygous Arg variant patients. The rate of aortic dissection over time was significantly higher for carriers of the Arg allele (p = 0.004). Additionally, Arg allele carriers were more likely to reach the combined endpoint of dissection or death (p = 0.03). CONCLUSIONS: We demonstrate the marked adverse impact of the 719Arg variant of the KIF6 gene on the likelihood that a TAA patient will suffer aortic dissection. Clinical assessment of the variant status of this molecularly important gene may provide a valuable "non-size" criterion to enhance surgical decision making above and beyond the currently used metric of aortic size (diameter).

Ectopic Expression of PvHMA2.1 Enhances Cadmium Tolerance in Arabidopsis thaliana.

Cadmium (Cd) in soil inhibits plant growth and development and even harms human health through food chain transmission. Switchgrass (Panicum virgatum L.), a perennial C4 biofuel crop, is considered an ideal plant for phytoremediation due to its high efficiency in removing Cd and other heavy metals from contaminated soil. The key to understanding the mechanisms of switchgrass Cd tolerance is to identify the genes involved in Cd transport. Heavy-metal ATPases (HMAs) play pivotal roles in heavy metal transport, including Cd, in Arabidopsis thaliana and Oryza sativa, but little is known about the functions of their orthologs in switchgrass. Therefore, we identified 22 HMAs in switchgrass, which were distributed on 12 chromosomes and divided into 4 groups using a phylogenetic analysis. Then, we focused on PvHMA2.1, which is one of the orthologs of the rice Cd transporter OsHMA2. We found that PvHMA2.1 was widely expressed in roots, internodes, leaves, spikelets, and inflorescences, and was significantly induced in the shoots of switchgrass under Cd treatment. Moreover, PvHMA2.1 was found to have seven transmembrane domains and localized at the cell plasma membrane, indicating that it is a potential transporter. The ectopic expression of PvHMA2.1 alleviated the reduction in primary root length and the loss of fresh weight of Arabidopsis seedlings under Cd treatment, suggesting that PvHMA2.1 enhanced Cd tolerance in Arabidopsis. The higher levels of relative water content and chlorophyll content of the transgenic lines under Cd treatment reflected that PvHMA2.1 maintained water retention capacity and alleviated photosynthesis inhibition under Cd stress in Arabidopsis. The roots of the PvHMA2.1 ectopically expressed lines accumulated less Cd compared to the WT, while no significant differences were found in the Cd contents of the shoots between the transgenic lines and the WT under Cd treatment, suggesting that PvHMA2.1 reduced Cd absorption from the environment through the roots in Arabidopsis. Taken together, our results showed that PvHMA2.1 enhanced Cd tolerance in Arabidopsis, providing a promising target that could be engineered in switchgrass to repair Cd-contaminated soil.

Degradation of polymeric polyproanthocyanidins from black chokeberry by microwave-assisted nucleophilic technique of sulfite/catechin: Reaction kinetics, antioxidation and structural analysis.

Microwave was employed to enhance the degradation of polymeric proanthocyanidins from black chokeberry using the nucleophilic technique of sulfite/catechin. Based on the degradation effect and kinetics, it was found that increasing the microwave time, microwave power, microwave temperature, sulfite concentration, and mass ratio of raw material to catechins was favourable for the degradation reaction. The degradation kinetics conformed to a random first-order degradation model. The antioxidant activity of the degraded products was analysed using DPPH and O2- assay, which suggested that the scavenging effect of the products was improved. FT-IR and 1H NMR analyses showed that the main functional groups were not destroyed. Using MALDI-TOF/MS to study the components of the degradation products, it was found that the molecular weight distribution became narrower, and the compositions were more single. Polyproanthocyanidins were reduced to oligomers. This study suggested that microwave-assisted nucleophilic techniques could produce oligomeric proanthocyanidins with remarkably improved functionalities.

Diagnostic performance of DCE-MRI, multiparametric MRI and multimodality imaging for discrimination of breast non-mass-like enhancement lesions.

OBJECTIVE: The aim of this study was to investigate and compare the diagnostic performance of dynamic contrast-enhanced (DCE)-MRI, multiparametric MRI (mpMRI), and multimodality imaging (MMI) combining mpMRI and mammography (MG) for discriminating breast non-mass-like enhancement (NME) lesions. METHODS: This retrospective study enrolled 193 patients with 199 lesions who underwent 3.0 T MRI and MG from January 2017 to December 2019. The features of DCE-MRI, turbo inversion recovery magnitude (TIRM), and diffusion-weighted imaging (DWI) were assessed by two breast radiologists. Then, all lesions were divided into microcalcification and non-microcalcification groups to assess the features of MG. Comparisons were performed between groups using univariate analyses. Then, multivariate analyses were performed to construct diagnostic models for distinguishing NME lesions. Diagnostic performance was evaluated by using the area under the curve (AUC) and the differences between AUCs were evaluated by using the DeLong test. RESULTS: Overall (n = 199), mpMRI outperformed DCE-MRI alone (AUCmpMRI = 0.924 vs. AUCDCE-MRI = 0.884; p = 0.007). Furthermore, MMI outperformed both mpMRI and MG (the microcalcification group [n = 140]: AUCMMI = 0.997 vs. AUCmpMRI = 0.978, p = 0.018 and AUCMMI = 0.997 vs. AUCMG = 0.912, p < 0.001; the non-microcalcification group [n = 59]: AUCMMI = 0.857 vs. AUCmpMRI = 0.768, p = 0.044 and AUCMMI = 0.857 vs. AUCMG = 0.759, p = 0.039). CONCLUSION & ADVANCES IN KNOWLEDGE: DCE-MRI combined with DWI and TIRM information could improve the diagnostic performance for discriminating NME lesions compared with DCE-MRI alone. Furthermore, MMI combining mpMRI and MG showed better discrimination than both mpMRI and MG.

Global Research Trends on the Treatment of Diffuse Large B-Cell Lymphoma: A Bibliometric and Visualized Study.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype. Treatment of DLBCL has improved greatly in recent decades, with thousands of papers published. We conducted a bibliometric analysis of the literature on DLBCL treatment, and discussed cooperation among authors, countries, and institutions, and identified research hotspots for DLBCL treatment. We searched the Web of Science Core Collection (WOSCC) using "Diffuse Large B Cell Lymphoma or DLBCL" and "Treatment or Therapy or Clinical Trial" as the subject terms, and analyzed the publication year, research direction, country/region, institution, author, source publication, distribution of funding institutions, and other conditions provided by the database. In addition, scientometrics software was used to analyze literature citations and cooperative publications. Bibliometric analyses were performed using https://bibliometric.com/app and VOSviewer. Network maps were generated to evaluate collaborations between different authors, countries, institutions, and keywords. A total of 7,255 studies on treatment of DLBCL were retrieved from the WOSCC on February 19, 2021. We found that the number of publications increased gradually from 1999 to 2021, and this trend was relatively stable in the past 3 years. The countries that produced the most publications were the United States, China, and Japan. Among institutions, University of Texas MD Anderson Cancer Center published the most manuscripts. Furthermore, the United States also had the most annual publications, citations, distribution of journal sources, and funding. Cooperative research between countries is also relatively important to treatment of DLBCL. Therapeutic regimens such as CHOP and R-CHOP, and immunotherapy (CAR-T, PD1/PDL1, and CAR-NK, etc.), have received increased attention. Bibliometric analysis of studies related to DLBCL treatment can help researchers and clinical workers quickly understand the hotspots and development trends in this field, and provide reference for the formulation of public health policies.

The Impact of Vapor Blockage on the Outflow Rate of Screen Channel Liquid Acquisition Devices.

The outflow rate of screen channel liquid acquisition devices (LADs) is a key indicator of the liquid acquisition capacity, but would be decreased when a portion of its screen is blocked by the vapor. So far, the quantitative research about the consequent loss of outflow rate seems not enough, though it is important and inevitable. In this paper, a modified model by introducing an "available rate" to describe the blocked degree is established to analyze and compare the cases with and without vapor blockage. We found that the loss of outflow rate is mainly decided by the total area of the blocked screen, while the distribution of blockage position barely has any effects. Besides, a "characteristic curve" is proposed to describe the robustness of LAD against blockage (i.e., loss rate of outflow velocity versus total area of the blocked screen). Higher driving pressure, coarser mesh of screen, and higher ratio of length to height of the channel would bring about greater robustness.

Syntenin Regulated by miR-216b Promotes Cancer Progression in Pancreatic Cancer.

Outcomes for patients with pancreatic cancer (PC) are poor; therefore, there is an urgent need to identify novel therapeutic targets involved in the progression of PC. We previously identified 161 differentially expressed proteins (DEPs) in PC. Syntenin (SDCBP) was identified as a survival-related protein through integrated, survival, and Cox analyses. High expression of SDCBP was associated with a poor prognosis in PC tissue and promoted the proliferation, migration, and invasion of PC cells, and induced epithelial-mesenchymal transition (EMT) via the PI3K/AKT pathway. Additionally, we elucidated the regulatory mechanism underlying these roles of SDCBP at the post-transcriptional level. microRNAs (miRNAs) of SDCBP were predicted using bioinformatics. Low levels of miR-216b expression were confirmed in PC tissues and were negatively correlated with SDCBP expression. miR-216b was found to directly regulate SDCBP expression through luciferase reporter assays. Furthermore, agomiR-216b restrained PC proliferation, migration, invasion, and EMT via the PI3K/AKT pathway, whereas antagomiR-216b facilitated this process. Notably, the knockout of SDCBP counteracted the effect of antagomiR-216b in PC, which suggested that miR-216b and SDCBP represent molecular targets underlying PC progression and EMT. Finally, the results were validated in in vivo studies. These findings indicated that low expression of miR-216b and the oncogene SDCBP contributes to PC migration, invasion, and EMT, and that they have potential as future therapeutic targets for patients with PC.

Primary Mediastinal B-Cell Lymphoma: Novel Precision Therapies and Future Directions.

Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct clinicopathologic disease from other types of diffuse large B-cell lymphoma (DLBCL) with unique prognostic features and limited availability of clinical data. The current standard treatment for newly diagnosed PMBCL has long been dependent on a dose-intensive, dose-adjusted multi-agent chemotherapy regimen of rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH). Recent randomized trials have provided evidence that R-CHOP followed by consolidation radiotherapy (RT) is a valuable alternative option to first-line treatment. For recurrent/refractory PMBCL (rrPMBCL), new drugs such as pembrolizumab and CAR-T cell therapy have proven to be effective in a few studies. Positron emission tomography-computed tomography (PET-CT) is the preferred imaging modality of choice for the initial phase of lymphoma treatment and to assess response to treatment. In the future, baseline quantitative PET-CT can be used to predict prognosis in PMBCL. This review focuses on the pathology of PMBCL, underlying molecular basis, treatment options, radiotherapy, targeted therapies, and the potential role of PET-CT to guide treatment choices in this disease.

Identification of a competing endogenous RNA axis related to gastric cancer.

Competing endogenous RNA (ceRNA) pathways play pivotal roles in the formation and progression of gastric cancer (GC). Employing multi-omics analysis, we sought to identify a ceRNA network associated with GC progression. We analyzed3Gene Expression Omnibus datasets as well as data from The Cancer Genome Atlas to identify genes that were differentially expressed in GC tissues. A total of 84 upregulated genes and 106 downregulated genes were found. Enrichment analysis indicated that some pathways were strongly linked with tumor formation and progression. We also screened hub genes to establish a lncRNA-miRNA-mRNA network. We ultimately identified 8 hub genes, 6 key miRNAs and 4 key lncRNAs that interact within a common ceRNA network. Correlation analysis and in vitro experiments were conducted to verify the regulatory effect of the ceRNA network in GC. A knockdown assay confirmed that the DLGAP1-AS1/miR-203a-3p/THBS2 axis is a ceRNA network involved in GC progression. In this study, we elucidated the role of the DLGAP1-AS1/miR-203a-3p/THBS2 ceRNA network in the progression of GC. These molecules maybe evaluated as therapeutic targets and prognostic biomarkers for GC.

CPA4 Promotes EMT in Pancreatic Cancer via Stimulating PI3K-AKT-mTOR Signaling.

BACKGROUND: Carboxypeptidase A4 (CPA4), as a novel tumor biomarker, is prevalently observed in various cancers. However, the potential role of CPA4 in pancreatic cancer (PC), to our knowledge, has not been fully clarified. MATERIALS AND METHODS: We systematically explored the detailed function of CPA4 in epithelial to mesenchymal transition (EMT) stimulated PC in human clinical samples and in vitro. RESULTS: CPA4 was overexpressed in clinical PC samples that was positively related with tumor size (P=0.026), T stage (P=0.011), lymph-node metastasis (P=0.026) and a worse prognosis for PC patients (P=0.001). Interestingly, CPA4 was inversely correlated with E-cadherin (r=-0.372, P=0.003) in clinical samples and PC cell lines which cooperatively contributed to a worse prognosis (P=0.005) for PC patients. CPA4 overexpression enhanced EMT in AsPC-1 and Capan-2 cells, which promoted EMT-like cellular morphology and cell invasion and migration. Meanwhile, CPA4 overexpression activated EMT and PI3K-AKT-mTOR signaling, following with the downregulation of E-cadherin and ß-catenin, and the upregulation of N-cadherin, vimentin, p-PI3K (Tyr458), p-AKT (Ser473) and p-mTOR (Ser2448). However, PI3K inhibitor LY294002 reversed CPA4 overexpression-stimulated EMT in vitro. Moreover, CPA4 was co-immunoprecipitated with AKT in two PC cells with CPA4 high expression. Conversely, CPA4 silencing inhibited EMT in PANC-1 cells. CPA4 overexpression or silencing promoted or inhibited cell proliferation and drug resistance in Capan-2 and PANC-1 cells via regulating Bcl2/Bax and cleaved-caspase3 signaling. However, LY294002 reversed CPA4 overexpression-stimulated cell proliferation and drug resistance in vitro in Bcl2/Bax and caspase3-dependent apoptosis. CONCLUSION: CPA4 overexpression contributes to aggressive clinical stage of PC patients and promotes EMT in vitro via activation of PI3K-AKT-mTOR signaling.

Serratane triterpenoids from Lycopodium complanatum and their anti-cancer and anti-inflammatory activities.

Phytochemical investigation of the ethyl acetate fraction of Lycopodium complanatum led to eight new serratane triterpenoids (lycomplanatums A-H, 1-8), along with five known analogues (9-13). Their structures were elucidated by extensive spectroscopic methods, including 1D/2D NMR, HRESIMS, and DFT GIAO 13C NMR calculation. Among them, compounds 2 and 13 showed moderate antiproliferative effects against seven human cancer cell lines, especially for MCF-7 with IC50 values of 13.8-44.7 µM. Additionally, the compounds were screened for anti-inflammatory effects based on their inhibitory activities of nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 cells, and compounds 2 and 13 diminished NO production more potently than others in a concentration-dependent manner.

Overexpression of MsASMT1 Promotes Plant Growth and Decreases Flavonoids Biosynthesis in Transgenic Alfalfa (Medicago sativa L.).

Melatonin (N-acetyl-5-methoxytryptamine) is a pleiotropic signaling molecule that plays important roles in plant growth, development and stress responses. Alfalfa (Medicago sativa L.) is an important and widely cultivated leguminous forage crop with high biomass yield and rich nutritional value. The effects of exogenous melatonin content regulation on alfalfa stress tolerance have been investigated in recent years. Here, we isolated and introduced the MsASMT1 (N-acetylserotonin methyltransferase) gene into alfalfa, which significantly improved the endogenous melatonin content. Compared with wild-type (WT) plants, MsASMT1 overexpression (OE-MsASMT1) plants exhibited a series of phenotypic changes, including vigorous growth, increased plant height, enlarged leaves and robust stems with increased cell sizes, cell numbers and vascular bundles, as well as more branches. We also found that the flavonoid content and lignin composition of syringyl to guaiacyl ratio (S/G) were decreased and the cellulose content was increased in OE-MsASMT1 transgenic alfalfa. Further transcriptomic and metabolomic exploration revealed that a large group of genes in phenylalanine pathway related to flavonoids and lignin biosynthesis were significantly altered, accompanied by significantly reduced concentrations of the glycosides of quercetin, kaempferol, formononetin and biochanin in OE-MsASMT1 transgenic alfalfa. Our study first uncovers the effects of endogenous melatonin on alfalfa growth and metabolism. This report provides insights into the regulation effects of melatonin on plant growth and phenylalanine metabolism, especially flavonoids and lignin biosynthesis.

Oxymatrine protects against l-arginine-induced acute pancreatitis and intestine injury involving Th1/Th17 cytokines and MAPK/NF-κB signalling.

Context: Oxymatrine (OMT) has various pharmacological effects, including immune reaction regulation, anti-inflammation and anti-hypersensitive reaction. Objective: This is the first report to investigate the molecular mechanism of OMT function in l-arginine (Arg)-induced acute pancreatitis (AP) involving intestinal injury. Materials and methods: Rat pancreatic AR42J and small intestinal IEC-6 cells were treated with Arg (200-800 µM) for 48 h plus OMT (4 mg/mL) treatment. Thirty adult Wistar rats were randomly assigned to control (saline), AP (i.p. of 250 mg/100 g body weight Arg) and OMT (i.p. injection of 50 mg/kg b.w. OMT every 6 h following Arg). Both cells and rats were harvested at 48 h. Results: Arg-induced cell proliferation in both rats AR42J (EC50 633.9 ± 31.4 µM) and IEC-6 cells (EC50 571.3 ± 40.4 µM) in a dose-dependent manner, which was significantly inhibited by OMT (4 mg/mL). Meanwhile, Arg (600 µM) induced expression of proinflammatory cytokines (TNF-α, IL-6, IL-1ß, NF-κB, IL-17A/IL-17F and IFN-γ) and activation of p-p38/p-ERK in vitro, which was reversed by OMT. In vivo, OMT (50 mg/kg) inhibited 250 mg/100 g of Arg-induced AP involving intestinal injury, including inhibiting Arg-induced inflammatory in pancreas and intestine, inhibiting Arg-induced increase of TNF-α, IL-6, IL-1ß, NF-κB and p-p38/p-ERK-MAPK signalling, and inhibiting Arg-induced increase of IL-17A/IL-17F, IFN-γ, ROR-γt and T-bet. Meanwhile, OMT inhibited Arg-induced expression of CD44 and CD55 in intestinal injury. Discussion and conclusions: OMT protects against Arg-induced AP involving intestinal injury via regulating Th1/Th17 cytokines and MAPK/NF-κB signalling, which is a promising therapeutic agent in clinics.

Cognitive flexibility impairment and reduced frontal cortex BDNF expression in the ouabain model of mania.

Central infusion of the Na+/K+-ATPase inhibitor, ouabain in rats serves as an animal model of mania because it leads to hyperactivity, as well as reproduces ion dysregulation and reduced brain-derived neurotrophic factor (BDNF) levels similar to that observed in bipolar disorder. Bipolar disorder is also associated with cognitive inflexibility and working memory deficits. It is unknown whether ouabain treatment in rats leads to similar cognitive flexibility and working memory deficits. The present study examined the effects of an intracerebral ventricular infusion of ouabain in rats on spontaneous alternation, probabilistic reversal learning and BDNF expression levels in the frontal cortex. Ouabain treatment significantly increased locomotor activity, but did not affect alternation performance in a Y-maze. Ouabain treatment selectively impaired reversal learning in a spatial discrimination task using an 80/20 probabilistic reinforcement procedure. The reversal learning deficit in ouabain-treated rats resulted from an impaired ability to maintain a new choice pattern (increased regressive errors). Ouabain treatment also decreased sensitivity to negative feedback during the initial phase of reversal learning. Expression of BDNF mRNA and protein levels was downregulated in the frontal cortex which also negatively correlated with regressive errors. These findings suggest that the ouabain model of mania may be useful in understanding the neuropathophysiology that contributes to cognitive flexibility deficits and test potential treatments to alleviate cognitive deficits in bipolar disorder.