Colchicine protects against acute pancreatitis via downregulation of cytokine levels

Purpose: To investigate the effect of colchicine on acute pancreatitis (AP) in a rat model, and the molecular mechanism involved. Methods: Acute pancreatitis (AP) was induced in rats by injection with 5 % sodium taurocholate. Changes in histology of pancreatic tissues were determined following treatment with colchicine. Serum amylase activity was measured using Automated Biochemistry Analyser. Results: Hematoxylin and eosin (H & E) staining showed that colchicine prevented histopathological changes such as infiltration of interstitial leukocytes and erythrocytes, cell necrosis, oedema formation and vacuolization in the rat pancreas. Treatment of AP rats with colchicine significantly and dosedependently decreased ascite volume in the abdominal cavity. Serum amylase activity was significantly suppressed in AP rats on treatment with 100 mg/kg colchicine. Furthermore, treatment of the AP rats with colchicine caused marked decrease in the expressions of interleukin 6 and tumor necrosis factor α, and upregulated expressions of IL 10 in serum. Colchicine treatment of AP rats also caused significant increase in CGRP level in the plasma. Conclusion: Colchicine prevents pancreatic tissue damage induced by AP by down-regulating proinflammatory cytokines, upregulation of anti-inflammatory cytokines, and enhancing CGRP release. Therefore, colchicine may be useful for the treatment of acute pancreatitis

Few-Shot Classification With Feature Reconstruction Bias

Few-shot classification aims to classify unseen samples by learning from very few labeled samples. Very recently, reconstruction-based methods have been proposed and shown superior performance on few-shot fine-grained image classification, which, on top of the challenge of few labeled samples, faces the difficulty of identifying subtle differences between sub-categories. In essence, these methods reconstruct unseen samples from few seen samples and use the distance between the original unseen samples and their reconstruction as the criterion for classification. However, as pointed out in this paper, a bias is introduced in the overall distribution between the reconstructed features and original features, which consequently affects the distance calculation and subsequent classification. To address this issue, we propose a new concept of Feature Reconstruction Bias (FRB), which can be computed easily in the training stage without introducing any new parameters. Moreover, we propose to use this bias to correct query features in the test stage, which is shown to increase inter-class distances and decrease intra-class distances. Experiments on four fine-grained benchmarks demonstrate the effectiveness of our approach, with state-of-the-art performance achieved in most scenarios

Dual drug delivery from hydrophobic and hydrophilic intraocular lenses: in-vitro and in-vivo studies

Posterior capsule opacification (PCO) still remains the most frequent long term complication after cataract surgery, while endophthalmitis is rare but severe and should be prevented at all cost. Intraocular lenses (IOLs) with different designs (eg. edge and body-haptics angle) and materials (acrylic hydrophobic and acrylic hydrophilic surfaces) have been studied to reduce PCO. For the prevention of endophthalmitis, intracameral injection followed or not by topical treatment with antibiotics and anti-inflammatories are usually prescribed. The objective of this work was to investigate the use of IOLs as controlled release platforms of two drugs, the antibiotic moxifloxacin (MXF) and the anti-inflammatory ketorolac (KTL) that could advantageously substitute the usual treatment. Two types of IOLs were chosen, hydrophobic and hydrophilic. Hydrophobic IOLs have shown better results in the prevention of PCO because they adhere better to the posterior capsular bag, while hydrophilic IOLs are advised in the case of patients with uveitis, glaucoma or diabetes. The IOLs were loaded with MXF + KTL and sterilized by high hydrostatic pressure. Both IOLs reduced the tendency for adhesion of LECs. In vivo tests were done to compare the concentration of the drugs in the aqueous humor obtained after eye drops administration and drug-loaded IOLs implantation. The developed IOLs were able to release MXF and KTL at therapeutic levels, in a sustained way, which contrasts with the eye drops prophylaxis. No PCO signs were detected and histological analyses demonstrated biocompatibility of these devices.publishe

Long-Term Organic Farming Manipulated Rhizospheric Microbiome and Bacillus Antagonism Against Pepper Blight (Phytophthora capsici)

Soil-borne diseases are often less severe in organic farms, possibly because of the recruitment of beneficial microorganisms by crops. Here, the suppressiveness of organic, integrated, and conventionally managed soils to pepper blight (Phytophthora capsici) was studied in growth chamber experiments. Disease incidence was 41.3 and 34.1% lower in the soil from an organic farming system than in either the soil from the integrated or from the conventional farming systems, respectively. Beta-diversity of rhizospheric microbial communities differed among treatments, with enrichment of Bacillus, Sporosarcina, Acidobacteria Gp5, Gp6, Gp22, and Ignavibacterium by the organic soil. Cultivation-dependent analysis indicated that 50.3% of in vitro antagonists of P. capsici isolated from the rhizosphere of healthy peppers were affiliated to Bacillus. An integration of in vitro antagonists and bacterial diversity analyses indicated that Bacillus antagonists were higher in the rhizosphere of pepper treated by the organic soil. A microbial consortium of 18 in vitro Bacillus antagonists significantly increased the suppressiveness of soil from the integrated farming system against pepper blight. Overall, the soil microbiome under the long-term organic farming system was more suppressive to pepper blight, possibly owing to Bacillus antagonism in the rhizosphere. This study provided insights into microbiome management for disease suppression under greenhouse conditions

Volatiles from cotton aphid (Aphis gossypii) infested plants attract the natural enemy Hippodamia variegata

The Aphis gossypii is a major threat of cotton worldwide due to its short life cycle and rapid reproduction. Chemical control is the primary method used to manage the cotton aphid, which has significant environmental impacts. Therefore, prioritizing eco-friendly alternatives is essential for managing the cotton aphid. The ladybird, Hippodamia variegata, is a predominant predator of the cotton aphid. Its performance in cotton plantation is directly linked to chemical communication, where volatile compounds emitted from aphid-infested plants play important roles in successful predation. Here, we comprehensively studied the chemical interaction between the pest, natural enemy and host plants by analyzing the volatile profiles of aphid-infested cotton plants using gas chromatography-mass spectrometry (GC-MS). We then utilized the identified volatile compounds in electrophysiological recording (EAG) and behavioral assays. Through behavioral tests, we initially demonstrated the clear preference of both larvae and adults of H. variegata for aphid-infested plants. Subsequently, 13 compounds, namely α-pinene, cis-3-hexenyl acetate, 4-ethyl-1-octyn-3-ol, β-ocimene, dodecane, E-β-farnesene, decanal, methyl salicylate, β-caryophyllene, α-humulene, farnesol, DMNT, and TMTT were identified from aphid-infested plants. All these compounds were electrophysiologically active and induced detectable EAG responses in larvae and adults. Y-tube olfactometer assays indicated that, with few exceptions for larvae, all identified chemicals were attractive to H. variegata, particularly at the highest tested concentration (100 mg/ml). The outcomes of this study establish a practical foundation for developing attractants for H. variegata and open avenues for potential advancements in aphid management strategies by understanding the details of chemical communication at a tritrophic level

Development and verification of a combined immune- and cancer-associated fibroblast related prognostic signature for colon adenocarcinoma

IntroductionTo better understand the role of immune escape and cancer-associated fibroblasts (CAFs) in colon adenocarcinoma (COAD), an integrative analysis of the tumor microenvironment was performed using a set of 12 immune- and CAF-related genes (ICRGs).MethodsUnivariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to establish a prognostic signature based on the expression of these 12 genes (S1PR5, AEN, IL20RB, FGF9, OSBPL1A, HSF4, PCAT6, FABP4, KIF15, ZNF792, CD1B and GLP2R). This signature was validated in both internal and external cohorts and was found to have a higher C-index than previous COAD signatures, confirming its robustness and reliability. To make use of this signature in clinical settings, a nomogram incorporating ICRG signatures and key clinical parameters, such as age and T stage, was developed. Finally, the role of S1PR5 in the immune response of COAD was validated through in vitro cytotoxicity experiments.ResultsThe developed nomogram exhibited slightly improved predictive accuracy compared to the ICRG signature alone, as indicated by the areas under the receiver operating characteristic curves (AUC, nomogram:0.838; ICRGs:0.807). The study also evaluated the relationships between risk scores (RS) based on the expression of the ICRGs and other key immunotherapy variables, including immune checkpoint expression, immunophenoscore (IPS), and microsatellite instability (MSI). Integration of these variables led to more precise prediction of treatment efficacy, enabling personalized immunotherapy for COAD patients. Knocking down S1PR5 can enhance the efficacy of PD-1 monoclonal antibody, promoting the cytotoxicity of T cells against HCT116 cells ((p<0.05).DiscussionThese findings indicate that the ICRG signature may be a valuable tool for predicting prognostic risk, evaluating the efficacy of immunotherapy, and tailoring personalized treatment options for patients with COAD

Monitoring the Process of Endostar-Induced Tumor Vascular Normalization by Non-contrast Intravoxel Incoherent Motion Diffusion-Weighted MRI

Tumor vascular normalization has been proposed as a new concept in anti-tumor angiogenesis, and the normalization window is considered as an opportunity to increase the effect of chemoradiotherapy. However, there is still a lack of a non-invasive method for monitoring the process of tumor vascular normalization. Intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM DW-MRI) is an emerging approach which can effectively assess microperfusion in tumors, without the need for exogenous contrast agents. However, its role in monitoring tumor vascular normalization still needs further study. In this study, we established a tumor vascular normalization model of CT26 colon-carcinoma-bearing mice by means of Endostar treatment. We then employed IVIM DW-MRI and immunofluorescence to detect the process of tumor vascular normalization at different times after treatment. We found that the D* values of the Endostar group were significantly higher than those of the control group on days 4, 6, 8, and 10 after treatment, and the f values of the Endostar group were significantly higher than those of the control group on days 6 and 8. Furthermore, we confirmed through analysis of histologic parameters that Endostar treatment induced the CT26 tumor vascular normalization window starting from day 4 after treatment, and this window lasted for 6 days. Moreover, we found that D* and f values were well correlated with pericyte coverage (r = 0.469 and 0.504, respectively; P < 0.001, both) and relative perfusion (r = 0.424 and 0.457, respectively; P < 0.001, both). Taken together, our findings suggest that IVIM DW-MRI has the potential to serve as a non-invasive approach for monitoring Endostar-induced tumor vascular normalization

Expression of the Inhibitory Receptor TIGIT Is Up-Regulated Specifically on NK Cells With CD226 Activating Receptor From HIV-Infected Individuals

Natural killer (NK) cells are important for maintenance of innate immune system stability and serve as a first line of defense against tumors and virus infections; they can act either directly or indirectly and are regulated via co-operation between inhibitory and stimulatory surface receptors. The recently reported inhibitory receptor, TIGIT, can be expressed on the NK cell surface; however, the expression level and function of TIGIT on NK cells during HIV infection is unknown. In this study, for the first time, we investigated the expression and function of TIGIT in NK cells from HIV-infected individuals. Our data demonstrate that the level of TIGIT is higher on NK cells from patients infected with human immunodeficiency virus (HIV) compared with HIV-negative healthy controls. TIGIT expression is inversely correlated with CD4+ T cell counts and positively correlated with plasma viral loads. Additionally, levels of the TIGIT ligand, CD155, were higher on CD4+ T cells from HIV-infected individuals compared with those from healthy controls; however, there was no difference in the level of the activating receptor, CD226, which recognizes the same ligands as TIGIT. Furthermore, TIGIT was found to specifically up-regulated on CD226+ NK cells in HIV-infected individuals, and either rIL-10, or rIL-12 + rIL-15, could induce TIGIT expression on these cells. In addition, high TIGIT expression inhibited the production of interferon-gamma (IFN-γ) by NK cells, while TIGIT inhibition restored IFN-γ production. Overall, these results highlight the important role of TIGIT in NK cell function and suggest a potential new avenue for the development of therapeutic strategies toward a functional cure for HIV