Comparative transcriptomic analysis reveals the molecular changes of acute pancreatitis in experimental models.

BACKGROUND: Acute pancreatitis (AP) encompasses a spectrum of pancreatic inflammatory conditions, ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure. Given the challenges associated with obtaining human pancreatic samples, research on AP predominantly relies on animal models. In this study, we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models. AIM: To investigate the shared molecular changes underlying the development of AP across varying severity levels. METHODS: AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide (LPS). Additionally, using Ptf1α to drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J- hM3/Ptf1α(cre) mice were administered Clozapine N-oxide to induce AP. Subsequently, we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus (GEO) database. RESULTS: Caerulein-induced AP showed severe inflammation and edema, which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis. Compared with the control group, RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model. Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway, TLR signaling pathway, and NF-κB signaling pathway, alongside elevated levels of apoptosis-related pathways, such as apoptosis, P53 pathway, and phagosome pathway. The significantly elevated genes in the TLR and NOD-like receptor signaling pathways, as well as in the apoptosis pathway, were validated through quantitative real-time PCR experiments in animal models. Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood, while TLR1, TLR7, RIPK3, and OAS2 genes exhibited marked elevation in human AP. The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP. The transgenic mouse model hM3/Ptf1α(cre) successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway, indicating that these pathways represent shared pathological processes in AP across different models. CONCLUSION: The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP, notably the MYD88 gene. Apoptosis holds a central position in the necrotic processes of AP, with TUBA1A and GADD45A genes exhibiting prominence in human AP.

An efficient numerical method on modified space-time sparse grid for time-fractional diffusion equation with nonsmooth data.

In this paper, we focus on developing a high efficient algorithm for solving d-dimension time-fractional diffusion equation (TFDE). For TFDE, the initial function or source term is usually not smooth, which can lead to the low regularity of exact solution. And such low regularity has a marked impact on the convergence rate of numerical method. In order to improve the convergence rate of the algorithm, we introduce the space-time sparse grid (STSG) method to solve TFDE. In our study, we employ the sine basis and the linear element basis for spatial discretization and temporal discretization, respectively. The sine basis can be divided into several levels, and the linear element basis can lead to the hierarchical basis. Then, the STSG can be constructed through a special tensor product of the spatial multilevel basis and the temporal hierarchical basis. Under certain conditions, the function approximation on standard STSG can achieve the accuracy order O(2-JJ) with O(2JJ) degrees of freedom (DOF) for d=1 and O(2Jd) DOF for d>1, where J denotes the maximal level of sine coefficients. However, if the solution changes very rapidly at the initial moment, the standard STSG method may reduce accuracy or even fail to converge. To overcome this, we integrate the full grid into the STSG, and obtain the modified STSG. Finally, we obtain the fully discrete scheme of STSG method for solving TFDE. The great advantage of the modified STSG method can be shown in the comparative numerical experiment.

Association between morphological features of necrotizing pancreatitis on endoscopic ultrasound and outcomes of the endoscopic transmural step-up approach.

OBJECTIVE: To investigate the association between necrotic collections on endoscopic ultrasound (EUS) and outcomes of the endoscopic transmural step-up approach in necrotizing pancreatitis (NP). METHODS: Adult NP patients who had undergone endoscopic transmural step-up approach, endoscopic transmural drainage or endoscopic transmural necrosectomy, were retrospectively enrolled, and divided into groups 1, 2 and 3 based on the amount of solid necrotic debris (quantified as a percentage of the total collection size of <30%, 30%-50%, and >50%). RESULTS: A total of 134 patients were included, of whom 52, 59 and 23 patients were categorized into groups 1, 2 and 3. Patients with more solid necrotic debris required more necrosectomy sessions (group 3 vs group 2 vs group 1: 2.0 vs 1.0 vs 1.0, P < 0.001), were more likely to experience stent occlusion (group 3 vs group 2 vs group 1: 34.8% vs 16.9% vs 9.6%, P = 0.011), and had a longer hospitalization (group 3 vs group 2 vs group 1: 40.0 d vs 28.0 d vs 25.5 d, P = 0.015). High procalcitonin level (adjusted odds ratio [aOR] 6.14, 95% confidence interval [CI] 1.40-26.94, P = 0.016) and any organ failure (aOR 11.51, 95% CI 2.42-54.78, P = 0.002) were independently associated with clinical failure of endoscopic transmural step-up approach. CONCLUSIONS: More solid necrotic debris on EUS is related to more necrosectomy sessions, higher incidence of stent occlusion and longer hospitalization. A nomogram combining procalcitonin and any organ failure performs well in predicting clinical failure of endoscopic transmural step-up approach.

Nomogram for the Prediction of 30-Day Readmission in Acute Pancreatitis.

BACKGROUND: A prediction model for 30-day readmission in patients with acute pancreatitis (AP) was needed. AIMS: To develop a nomogram to predict 30-day readmission in patients with AP and validate the usefulness of serum indicators after discharge for the prediction of 30-day readmission. METHODS: This was a retrospective cohort study enrolling patients with the first attack of AP. Baseline characteristics, clinical profiles, and serum indicators after discharge were compared. Multivariate logistic regression analysis and a nomogram were employed to determine the independent risk factors for 30-day readmission. RESULTS: A total of 7.32% (121/1653) of the patients were readmitted within 30 days after discharge. Different etiologies (biliary pancreatitis (adjusted odds ratio (AdjOR), 9.63; 95% confidence interval (CI), 1.28-72.52; P = 0.028), other causes (AdjOR, 9.37; 95% CI, 1.15-76.12, P = 0.026), mixed causes (AdjOR, 10.76; 95% CI, 1.27-91.35; P = 0.03) compared with alcoholic pancreatitis)), infected pancreatitis necrosis (IPN) (AdjOR, 2.3; 95% CI, 1.2-4.42; P = 0.013), total bilirubin level ≥ 20.5 µmol/L (AdjOR, 2.42; 95% CI, 1.23-4.77; P = 0.01), glucose level ≥ 6.1 mmol/L (AdjOR, 1.93; 95% CI, 1.16-3.19; P = 0.011), and albumin level < 40 g/L (AdjOR, 4.25; 95% CI, 2.44-7.41; P < 0.001) were independently associated with 30-day readmission. A nomogram incorporating these factors demonstrated good discrimination, calibration, and clinical utility. Serum indicators after discharge added predictive value compared with clinical variables alone (AUC, 0.78 vs. 0.685; P = 0.0001). CONCLUSIONS: The nomogram combining etiology, IPN, and serum indicators after discharge has favorable predictive performance for 30-Day readmission. The close monitoring and reexamination of serum indicators are essential for AP patients at high risk.

Efficient photocatalytic H2 evolution and Cr(VI) reduction under visible light using a novel Z-scheme SnIn4S8/CeO2 heterojunction photocatalysts.

Semiconductor photocatalysis technology is a promising method for hydrogen production and water pollution treatment. Here, the SnIn4S8/CeO2 (SISC) composites were fabricated by a stirring and calcination method, and the mass ratio of SnIn4S8 to CeO2 was optimized. The 50 wt% SISC heterojunction photocatalyst has the highest visible light catalytic activity. The degradation rate of hexavalent chromium (Cr (VI)) is 98.8% in 75 min of light irradiation, which is 2.48 times that of pure CeO2. Besides, the 50 wt% SISC composite photocatalyst also has the highest photocatalytic hydrogen production efficiency (0.6193 mmol g-1 h-1), which exhibits a higher photocatalytic activity than pure CeO2 and SnIn4S8. The enhanced photocatalytic performance can be attributed to the Z-scheme heterojunction structure between CeO2 and SnIn4S8, which can effectively separate and transfer photo-generated charges, thereby reducing the recombination of photo-generated carriers. We hope this work can provide ideas for constructing Z-scheme heterojunction structures and improving photocatalytic activity under visible light.

Role of gut microbiota on intestinal barrier function in acute pancreatitis.

Acute pancreatitis (AP) is a common gastrointestinal disorder. Approximately 15%-20% of patients develop severe AP. Systemic inflammatory response syndrome and multiple organ dysfunction syndrome may be caused by the massive release of inflammatory cytokines in the early stage of severe AP, followed by intestinal dysfunction and pancreatic necrosis in the later stage. A study showed that 59% of AP patients had associated intestinal barrier injury, with increased intestinal mucosal permeability, leading to intestinal bacterial translocation, pancreatic tissue necrosis and infection, and the occurrence of multiple organ dysfunction syndrome. However, the real effect of the gut microbiota and its metabolites on intestinal barrier function in AP remains unclear. This review summarizes the alterations in the intestinal flora and its metabolites during AP development and progression to unveil the mechanism of gut failure in AP.

Effect of Plant-Soil Feedback on Secondary Metabolites of Acanthopanax senticosus Seedlings / 中国实验方剂学杂志

Objective::To investigate the effects of plant-soil feedback on secondary metabolites in roots, stems and leaves of Acanthopanax senticosus seedlings. Method::One-year-old seedlings of A. senticosus were planted in the soil where no A. senticosus had been planted before (group 1), soil where A. senticosus had been planted for 3 years (group 2), and soil where A. senticosus had been planted for many years in the greenhouse pot experiment, and the secondary metabolites of its roots, stems and leaves were then analyzed. Result::L-Phenylalanine, 3, 4-dihydroxybenzoic acid, syringin, chlorogenic acid, caffeic acid, eleutheroside E, isofraxidin, rutin, hyperoside, and quercetin had significant differences in leaves and roots of A. senticosus seedlings in the soil of group 3, but there was no significant difference in chlorogenic acid and eleutheroside E in stem. Eleutheroside E, isofraxidin, rutin and hyperoside were not detected in the leaves of seedlings planted in group 3.Most of the secondary metabolites in the roots of A. senticosus seedlings showed positive feedback, while in the stems of Acanthopanax senticosus seedlings, caffeine, A. senticosus glycosides, hypericin and quercetin showed negative feedback, and most of the secondary metabolites in the leaves of A. senticosus seedlings showed positive feedback. Conclusion::The plant and soil showed different feedback in different parts of the growth process of A. senticosus seedlings, and the soil where A. senticosus had not been planted was more advantageous to the secondary metabolites of A. senticosus seedlings. The results of the study provide a basis for the study of the effect of plant-soil feedback on the A. senticosus, and provide the theoretical basis and technical support for the artificial cultivation of A. senticosus.

Effect of Plant and Soil Feedback on Antioxidant System of Acanthopanax senticosus / 中国实验方剂学杂志

Objective::To study the effect of plant-soil feedback on the antioxidant enzyme system of Acanthopanax senticosus seedlings, in order to elucidate the changes of plant-soil feedback on the antioxidant enzyme system of A. senticosus seedlings, and provide theoretical basis for revealing the reasons of plant-soil feedback. Method::Through the greenhouse pot experiment, plant height, leaf color value (SPAD), antioxidant enzymes [protein, superoxide dismutase(SOD), catalase(CAT), peroxidase(POD), aseorbateperoxidase(APX), malondialdehyde(MDA)] and yield and growth related indexes of soil without A. senticosus (group 1), soil with A. senticosus (group 2) for three consecutive years and soil with A. senticosus (group 3) for many years were measured respectively. Result::There were significant differences in plant height, SPAD, protein, SOD, CAT, POD, APX and MDA between seedlings of A. senticosus planted for three consecutive years (group 1), two successive years (group 2) and three successive years (group 3). The biomass, MDA, CAT, POD and SOD of A. senticosus seedlings in the soil without A. senticosus (group 1) were higher than those in the soil with A. senticosus (group 2 and 3), while the protein and APX were lower than those in the soil with A. senticosus (group 2 and 3). Conclusion::Plant and soil shows negative feedback regulation during the growth of A. senticosus seedlings, which reduced the activity of antioxidant enzymes. Therefore, the soil without planting A. senticosus has more advantages for the growth of A. senticosus seedlings. The results provide a basis for explaining the effect of plant-soil feedback on the growth of A. senticosus, and a theoretical basis and technical support for the technical standards of A. senticosus cultivation in farmland.

Effect of Nitrogen Application on Antioxidant Enzyme System of Acanthopanax senticosus / 中国实验方剂学杂志

Objective::To study the effect of different N application rates on the growth and development of Acanthopanax senticosus and the changes of antioxidant enzyme activity, and screen out the suitable amount of nitrogen fertilizer for its growth and development, in order to provide scientific evidence for rational fertilization of Acanthopanax senticosus in artificial cultivation. Method::By single-point, single-factor field experiment, the study samples were one-year-old seedlings of growing evenly A. senticosus.Five nitrogen application treatment groups were set up in the fields.They were N1 (30 g·m-2), N2 (60 g·m-2), N3 (90 g·m-2), N4 (120 g·m-2), N5 (150 g·m-2) and CK (0 g·m-2) in the control group.Three months later, the raw weight of plant, root, leaf and stem were measured at harvest time.After drying to constant weight, plant dry weight, stem dry weight, leaf dry weight and root dry weight were measured.Fresh leaves of plants were collected to measure malondialdehyde(MDA) content and activities of catalase(CAT), superoxide dismutase(SOD), peroxidase(POD), acid phosphatase(ACP) and aseorbateperoxidase(APX) after harvesting seedlings. Result::The biomass of A. senticosus in group N4 (120 g·m-2) was the highest, the protein content in group N3 (90 g·m-2) was the highest, and the activity of all antioxidant enzymes in group N3 (90 g·m-2) was the lowest. Conclusion::There is a dose-effect relationship between seedlings and the nitrogen application rate.That is to say, low nitrogen application rate and high nitrogen application rate will cause stress on Acanthopanax senticosus, and the activity of antioxidant enzymes under low nitrogen application rate is higher than that under high nitrogen application rate.

Effect of Nitrogen Fertilizer on Carbon Metabolism and Growth and Development of Acanthopanax senticosus Seedlings / 中国实验方剂学杂志

Objective::To study the effect of different nitrogen application rates on the growth and carbon metabolism of Acanthopanax senticosus seedlings, and screen out the rational fertilization conditions, in order to provide basis and guidance for scientific fertilization of artificially cultivated A. senticosus. Method::A single-point, single-factor field experiment was conducted to study the seedlings of growing evenly A. senticosus.Five different nitrogen application treatment groups were set up to treat the seedlings, namely N1 group (30 g·m-2), N2 group (60 g·m-2), N3 group (90 g·m-2), N4 group (120 g·m-2), N5 group (150 g·m-2) and CK group (0 g·m-2), respectively.Three months later, plant height, root circumference, stem circumference, root-shoot ratio and SPAD were measured at harvest time.The contents of protein, sucrose, starch, soluble sugar and reducing sugar in fresh leaves were measured. Result::N3 treatment was the best treatment method for the growth and development of A. senticosus seedlings, and the growth of A. senticosus seedlings was the best under this treatment.The protein content of A. senticosus seedlings in N3 treatment was the highest.Starch and sucrose were best accumulated in N5 treatment group and CK treatment group.N5 treatment had the highest soluble sugar content and reducing sugar content. Conclusion::There is a dose-effect relationship between the growth and development of A. senticosus seedlings; that is to say, low and high nitrogen application treatments will cause stress on A. senticosus seedlings.In conclusion, the suitable nitrogen application rate for A. senticosus growth is 90-120 g·m-2.

RACK1 Acts as a Potential Tumor Promoter in Colorectal Cancer.

BACKGROUND: The receptor of activated protein kinase C 1 (RACK1) promotes the progression and invasion of several cancers. However, the role of RACK1 in the pathogenesis of colorectal cancer (CRC) has not been clearly defined. Herein, we aimed to investigate the biological role of RACK1 in CRC. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) dataset were searched, and the expression of RACK1 in CRC tissues and adjacent normal tissues was evaluated. Immunohistochemical staining was performed to detect the expression of RACK1 in human CRC, adenoma, and normal tissues. Western blotting was used to detect the expression of RACK1 in human CRC cell lines. Functional assays, such as BrdU, colony formation, and wound healing and transwell invasion assays, were used to explore the biological role of RACK1 in CRC. RESULTS: RACK1 was upregulated in CRC tissues compared with its expression in adjacent normal tissues in TCGA and the GEO dataset (P < 0.05). Moreover, RACK1 was significantly overexpressed in CRC and adenoma tissues compared with its expression in normal tissues (P < 0.05). Loss-of-function experiments showed that RACK1 promoted cell proliferation, migration, and invasion in vitro. CONCLUSIONS: Our data indicated that RACK1, as an oncogene, markedly promoted the progression of CRC, which suggested that RACK1 is a potential therapeutic target for CRC management.

Downregulation of tumor suppressor RACK1 by Helicobacter pylori infection promotes gastric carcinogenesis through the integrin ß-1/NF-κB signaling pathway.

Receptor of activated protein kinase C 1 (RACK1) is downregulated in gastric cancer and is involved in modulating NF-κB signaling pathway activity. However, the underlying molecular mechanisms regulating RACK1 expression are unclear. In this study, we demonstrated that downregulated expression of RACK1 was observed in gastric cancer tissue compared to adjacent normal tissue and was correlated with poor prognosis in patients. Helicobacter pylori (H. pylori) infection downregulated RACK1 expression in concert with canonical NF-κB signaling pathway activation in vivo and in vitro. RACK1 overexpression suppressed NF-κB signaling pathway activation as well as the release of downstream proinflammatory cytokines. In addition, RACK1 downregulation increased integrin ß-1 expression, while integrin ß-1 silencing decreased NF-κB signaling activation. Moreover, H. pylori infection downregulated RACK1 but upregulated integrin ß-1 expression at the precancerous lesion stages in human subjects. Our data indicate that H. pylori infection promotes the upregulation of integrin ß-1 expression via downregulation of RACK1 expression, which subsequently leads to the elevated activation of the NF-κB signaling pathway, an essential step in H. pylori-induced carcinogenesis.

Effect of electro-acupuncture combined with olfactory ensheathing cell transplantation on spinal cord injury axonal regeneration and direction / 中国骨伤

<p><b>OBJECTIVE</b>To explore the impact and mechanism of electro-acupuncture (EA) on olfactory ensheathing cells (OECs) transplantation of spinal cord injury (SCI) axonal regeneration.</p><p><b>METHODS</b>In the experiment, 72 adult Sprague Dawley male rats weighted (220±20) g underwent contusion and transection method to cause the T9 model of spinal cord injury, were randomly divided into four groups involving model group, EA group,OECs group,and EA+OECs group. 5% fluorescein gold (FG) solution of 0.5 µl was injected into rats' spinal cord at 4 weeks and 8 weeks after SCI, a series of tests were performed including fluorescein gold(FG) retrograde tagging, BBB scores.</p><p><b>RESULTS</b>(1)The BBB scores level among four groups had no differences from the 1st day to the 1st week after the SCI (P>0.05). From the 3rd week after the SCI, the BBB scores level in EA+ OECs group were obviously higher than that of other groups (P<0.05). (2)The result of the fluorescein gold (FG) retrograde tagging showed at 4 weeks and 8 weeks after treatment FG positive nerve fibers were observed in SCI region. In EA+OECs group the number of FG positive nerve fibers was more than other three groups, and the fibers were more regularly arranged than other three groups.</p><p><b>CONCLUSION</b>The combination of electro-acupuncture and OECs transplantation can recover the pathway of nerve conduction and promote nerve fibers regeneration and hind limb function recovery for SCI rat, and can guide the trend of the axonal regeneration.</p>

EGF enhances ADSCs secretion via ERK and JNK pathways.

The objective of this work was to study the effect of epidermal growth factor (EGF) induced secretions of angiogenesis factors in adipose-derived stem cells (ADSCs) and the involvement of mitogen-activated protein kinases (MAPK). ADSCs were cultured and ELISA assays were performed to quantify the vascular endothelial growth factor, the hepatocyte growth factor, and the stromal derived factor-1 in ADSC-conditioned medium before and after EGF treatments and after pharmacological inhibition of MAPKs with PD98059, SB203580, and SP600125. The tube formation assay was used to test the effects of EGF treated and inhibitor treated ADSCs on the human umbilical vein endothelial cells (HUVECs) tube formation. Liposuction was applied and ADSCs were cultured successfully. The ADSCs released a variety of angiogenic factors, with the EGF treatments enhancing secretions and promoting the HUVEC tube formation. The MAPK inhibitors PD98059 and SP600125 increased the paracrine to promote tubular formation, while the SB203580 played an opposite role. In conclusion, (1) the in vitro cultured ADSCs secrete various angiogenic factors and the EGF amplifies the secretion and can enhance the ADSCs on the HUVEC tube formation. (2) ERK1/2 and JNK pathway may be involved in the enhanced secretion capacity of ADSCs while the p38 pathway may exert an opposite effect.

[The effect of recombinant HSP47siRNA on the pathological scar in nude mice: in vivo study].

OBJECTIVE: To study the significance of HSP47 gene in the development of pathological scar. METHODS: The nude mice were used to reconstruct animal model of pathological scar. 16 days later, the mixture of recombinant HSP47siRNA and liposome was injected into the pathological scar in experimental group. In the control group, 0.25 ml PBS was injected intraperitoneally. 7 days after injection, the specimens were collected for detection of mRNA of HSP47, the collagen and for immunohistochemical study. RESULTS: In the control and experimental group, the collagen content was (91.71 +/- 1.24)% and (82.12 +/- 4.79)%, respectively; the expression of HSP47mRNA was 1 042 862.01 +/- 604 194.36 and 306 123.68 +/- 105 857.08, respectively; the expression of collagen I mRNA was 10 228 614.70 +/- 2 532 879.04 and 6 011 841.97 +/- 2 886 897.17, respectively;the scar volume was (255.60 +/- 21.34) mm3 and (132.99 +/- 24.06) mm3, respectively. All the above results showed significant difference between the two groups (P < 0.05). CONCLUSIONS: The collagen production can be reduced through suppression of the expression of HSP47 gene. It indicates that HSP47 gene enhance the development of keloid and could be used as the target of treatment.