Transcriptomic analysis reveals the potential crosstalk genes and immune relationship between Crohn's disease and atrial fibrillation.

Background: At present, there is a paucity of research on the link between Crohn's disease (CD) and atrial fibrillation (AF). Nevertheless, both ailments are thought to entail inflammatory and autoimmune processes, and emerging evidence indicates that individuals with CD may face an elevated risk of AF. To shed light on this issue, our study seeks to explore the possibility of shared genes, pathways, and immune cells between these two conditions. Methods: We retrieved the gene expression profiles of both CD and AF from the Gene Expression Omnibus (GEO) database and subjected them to analysis. Afterward, we utilized the weighted gene co-expression network analysis (WGCNA) to identify shared genes, which were then subjected to further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Furthermore, we employed a rigorous analytical approach by screening hub genes through both least absolute shrinkage and selection operator (LASSO) regression and support vector machine (SVM), and subsequently constructing a receiver operating characteristic (ROC) curve based on the screening outcomes. Finally, we utilized single-sample gene set enrichment analysis (ssGSEA) to comprehensively evaluate the levels of infiltration of 28 immune cells within the expression profile and their potential association with the shared hub genes. Results: Using the WGCNA method, we identified 30 genes that appear to be involved in the pathological progression of both AF and CD. Through GO enrichment analysis on the key gene modules derived from WGCNA, we observed a significant enrichment of pathways related to major histocompatibility complex (MHC) and antigen processing. By leveraging the intersection of LASSO and SVM algorithms, we were able to pinpoint two overlapping genes, namely CXCL16 and HLA-DPB1. Additionally, we evaluated the infiltration of immune cells and observed the upregulation of CD4+ and CD8+ T cells, as well as dendritic cells in patients with AF and CD. Conclusions: By employing bioinformatics tools, we conducted an investigation with the objective of elucidating the genetic foundations that connect AF and CD. This study culminated in the identification of CXCL16 and HLA-DPB1 as the most substantial genes implicated in the development of both disorders. Our findings suggest that the immune responses mediated by CD4+ and CD8+ T cells, along with dendritic cells, may hold a crucial role in the intricate interplay between AF and CD.

Safe Induction of Acute Inflammation with Enhanced Antitumor Immunity by Hydrogel-Mediated Outer Membrane Vesicle Delivery.

Acute inflammation has the potential for the recruitment of immune cells, inhibiting tumor angiogenesis, metastasis, and drug resistance thereby overcoming the tumor immunosuppressive microenvironment caused by chronic inflammation. Here, an acute inflammation inducer using bacteria outer membrane vesicles (OMVs) loaded in thermal-sensitive hydrogel (named OMVs-gel) for localized and controlled release of OMVs in tumor sites is proposed. OMVs trigger neutrophil recruitment and amplify acute inflammation inside tumor tissues. The hydrogel ensures drastic inflammation is confined within the tumor, addressing biosafety concerns that the direct administration of free OMVs may cause fatal effects. This strategy eradicated solid tumors safely and rapidly. The study further elucidates one of the possible immune mechanisms of OMVs-gel therapy, which involves the assembly of antitumor neutrophils and elastase release for selective tumor killing. Additionally, tumor vascular destruction induced by OMVs-gel results in tumor darkening, allowing for combinational photothermal therapy. The findings suggest that the use of OMVs-gel can safely induce acute inflammation and enhance antitumor immunity, representing a promising strategy to promote acute inflammation application in tumor immunotherapy.

The effect of ticagrelor on coronary microvascular function after PCI in patients with ACS compared to clopidogrel: A systematic review and meta-analysis.

BACKGROUND: The function of coronary microcirculation is an important factor in predicting the prognosis of patients with acute coronary syndrome (ACS) who receive percutaneous coronary intervention (PCI) therapy. Ticagrelor, a type of oral P2Y12 inhibitor, is widely prescribed to ACS patients and can improve prognosis compared to clopidogrel. However, the efficacy of ticagrelor on coronary microcirculation, compared to clopidogrel, remains unclear. The objective of this meta-analysis was to determine the efficacy of ticagrelor on coronary microcirculation. METHODS: The PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases were comprehensively searched to identify studies until November 2022. Data was pooled using the fixed effects model or random effects model based on the level of heterogeneity. Sensitivity analyses were performed to measure the effects of potential confounders. RESULTS: After screening, 16 trials with a total of 3676 participants were ultimately included in the analysis. The meta-analysis revealed that compared to clopidogrel, patients receiving ticagrelor exhibited a more significant reduction in the IMR (WMD: -6.23, 95% CI: -8.41 to -4.04), a reduction in the cTFC (WMD: -1.88; 95% CI: -3.32 to -0.45), and greater increases in CFR (WMD: 0.38; 95% CI: 0.18 to 0.57), MBG (RR 1.29, 95% CI 1.12 to 1.48), and TIMI (RR 1.03, 95% CI 1.00 to 1.06). CONCLUSION: Our findings suggest that, compared to clopidogrel, ticagrelor has a significant effect in reducing coronary microcirculatory resistance, enhancing coronary blood flow reserve, and improving myocardial perfusion.

LAMP2A, LAMP2B and LAMP2C: similar structures, divergent roles.

LAMP2 (lysosomal associated membrane protein 2) is one of the major protein components of the lysosomal membrane. There currently exist three LAMP2 isoforms, LAMP2A, LAMP2B and LAMP2C, and they vary in distribution and function. LAMP2A serves as a receptor and channel for transporting cytosolic proteins in a process called chaperone-mediated autophagy (CMA). LAMP2B is required for autophagosome-lysosome fusion in cardiomyocytes and is one of the components of exosome membranes. LAMP2C is primarily implicated in a novel type of autophagy in which nucleic acids are taken up into lysosomes for degradation. In this review, the current evidence for the function of each LAMP2 isoform in various pathophysiological processes and human diseases, as well as their possible mechanisms, are comprehensively summarized. We discuss the evolutionary patterns of the three isoforms in vertebrates and provide technical guidance on investigating these isoforms. We are also concerned with the newly arising questions in this particular research area that remain unanswered. Advances in the functions of the three LAMP2 isoforms will uncover new links between lysosomal dysfunction, autophagy and human diseases.Abbreviation: ACSL4: acyl-CoA synthetase long-chain family member 4; AD: Alzheimer disease; Ag: antigens; APP: amyloid beta precursor protein; ATG14: autophagy related 14; AVSF: autophagic vacuoles with unique sarcolemmal features; BBC3/PUMA: BCL2 binding component 3; CCD: C-terminal coiled coil domain; CMA: chaperone-mediated autophagy; CVDs: cardiovascular diseases; DDIT4/REDD1: DNA damage inducible transcript 4; ECs: endothelial cells; ER: endoplasmic reticulum; ESCs: embryonic stem cells; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GBA/ß-glucocerebrosidase: glucosylceramidase beta; GSCs: glioblastoma stem cells; HCC: hepatocellular carcinoma; HD: Huntington disease; HSCs: hematopoietic stem cells; HSPA8/HSC70: heat shock protein family A (Hsp70) member 8; IL3: interleukin 3; IR: ischemia-reperfusion; LAMP2: lysosomal associated membrane protein 2; LDs: lipid droplets; LRRK2: leucine rich repeat kinase 2; MA: macroautophagy; MHC: major histocompatibility complex; MST1: macrophage stimulating 1; NAFLD: nonalcoholic fatty liver disease; NFE2L2/NRF2: NFE2 like bZIP transcription factor 2; NLRP3: NLR family pyrin domain containing 3; PARK7: Parkinsonism associated deglycase; PD: Parkinson disease; PEA15/PED: proliferation and apoptosis adaptor protein 15; PKM/PKM2: pyruvate kinase M1/2; RA: rheumatoid arthritis; RARA: retinoic acid receptor alpha; RCAN1: regulator of calcineurin 1; RCC: renal cell carcinoma; RDA: RNautophagy and DNautophagy; RNAi: RNA interference; RND3: Rho Family GTPase 3; SG-NOS3/eNOS: deleterious glutathionylated NOS3; SLE: systemic lupus erythematosus; TAMs: tumor-associated macrophages; TME: tumor microenvironment; UCHL1: ubiquitin C-terminal hydrolase L1; VAMP8: vesicle associated membrane protein 8.

Bacterial outer membrane vesicles-based therapeutic platform eradicates triple-negative breast tumor by combinational photodynamic/chemo-/immunotherapy.

Bacterial outer membrane vesicles (OMVs) are potent immuno-stimulating agents and have the potentials to be bioengineered as platforms for antitumor nanomedicine. In this study, OMVs are demonstrated as promising antitumor therapeutics. OMVs can lead to beneficial M2-to-M1 polarization of macrophages and induce pyroptosis to enhance antitumor immunity, but the therapeutic window of OMVs is narrow for its toxicity. We propose a bioengineering strategy to enhance the tumor-targeting ability of OMVs by macrophage-mediated delivery and improve the antitumor efficacy by co-loading of photosensitizer chlorin e6 (Ce6) and chemotherapeutic drug doxorubicin (DOX) into OMVs as a therapeutic platform. We demonstrate that systemic injection of the DOX/Ce6-OMVs@M therapeutic platform, providing combinational photodynamic/chemo-/immunotherapy, eradicates triple-negative breast tumors in mice without side effects. Importantly, this strategy also effectively prevents tumor metastasis to the lung. This OMVs-based strategy with bioengineering may serve as a powerful therapeutic platform for a synergic antitumor therapy.

Adsorption Characteristics and Enrichment of Emodin from Marine-Derived Aspergillus flavipes HN4-13 Extract by Macroporous Resin XAD-16.

Emodin, a hydroxyanthraquinone derivative, has been used as medicine for more than 2000 years due to its extensive pharmacological activities. Large-scale production of emodin has been achieved by optimizing the fermentation conditions of marine-derived Aspergillus flavus HN4-13 in a previous study. However, the fermentation broth contained complex unknown components, which adversely affected the study of emodin. Herein, the conditions for the enrichment of emodin from A. flavipes HN4-13 extract using XAD-16 resin were optimized, and a separation method with high efficiency, simple operation, a low cost, and a large preparative scale was established. The adsorption process of emodin on the XAD-16 resin conformed to pseudo-second-order kinetics and Langmuir models. The optimal conditions for the adsorption process were as follows: An emodin concentration, flow rate, and loading volume of 0.112 mg/mL, 2 BV/h, and 10 BV, respectively. For desorption, 50% ethanol was used to elute impurities and 80% ethanol was used to desorb emodin. After enrichment with XAD-16 resin, the emodin content increased from 1.16% to 11.48%, and the recovery rate was 75.53% after one-step treatment. These results demonstrate the efficiency of the simple adsorption-desorption strategy, using the XAD-16 resin for emodin enrichment.

Hybrid Cell Membrane-Functionalized Biomimetic Nanoparticles for Targeted Therapy of Osteosarcoma.

PURPOSE: In order to prepare a biomimetic nano-carrier which has inflammatory chemotaxis, homologous targeting and reduce immune clearance, for targeted chemotherapy of osteosarcoma, we fabricated the paclitaxel-loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles coated with 143B-RAW hybrid membrane (PTX-PLGA@[143B-RAW] NPs) and evaluate its anti-cancer efficacy in vitro and vivo. METHODS: PTX-PLGA@[143B-RAW] NPs were prepared by the ultrasonic method and were characterized by size, zeta potential, polymer dispersion index (PDI), Coomassie bright blue staining, transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC). Cellular uptake, cell viability assay, flow cytometry and chemotactic effect of PTX-PLGA@[143B-RAW] NPs were evaluated in vitro. Biodistribution, anti-cancer therapeutic efficacy and safety of PTX-PLGA@[143B-RAW] NPs were evaluated in 143B osteosarcoma xenograft mice. RESULTS: The hybrid membrane successfully coated onto the surface of PLGA nanoparticles. PTX-PLGA@[143B-RAW] NPs had a drug loading capacity of 4.24 ± 0.02% and showed targeting ability to osteosarcoma. PTX-PLGA@[143B-RAW] NPs showed high cellular uptake and improved anti-cancer efficacy against 143B cells. More importantly, PTX-PLGA@[143B-RAW] NPs treatment suppressed tumor growth in tumor-bearing mice with minimal damage to normal tissues. CONCLUSION: PTX-PLGA@[143B-RAW] NPs could be used for targeted drug delivery and osteosarcoma therapy.

Cobalt-Catalyzed Deprotection of Allyl Carboxylic Esters Induced by Hydrogen Atom Transfer.

A brief, efficient method has been developed for the removal of the allyl protecting group from allyl carboxylic esters using a Co(II)/TBHP/(Me2SiH)2O catalytic system. This facile strategy displays excellent chemoselectivity, functional group tolerance, and high yields. This transformation probably occurs through the hydrogen atom transfer process, and a Co(III)-six-membered cyclic intermediate is recommended.

Enhancement of Emodin Production by Medium Optimization and KH2PO4 Supplementation in Submerged Fermentation of Marine-Derived Aspergillus favipes HN4-13.

Emodin is a widely distributed anthraquinone derivative with a variety of biological activities, one that can be efficiently produced by marine-derived fungus Aspergillus favipes HN4-13. However, its relatively low fermentation yield limits further development and pharmaceutical research work. In this study, Plaekett-Burman design and central composite design were adopted to optimize the fermentation conditions of A. favipes HN4-13. Optimal fermentation conditions in a 250-mL Erlenmeyer flask with 50 mL of medium were 59.3 g/L soluble starch, 10 g/L yeast extract paste, 30 g/L seawater salt, 1.04 g/L KH2PO4, 0.05 g/L MgSO4·7H2O, 0.01 g/L FeSO4·7H2O, seed culture 24 h, pH 5, inoculum size 18%, culture temperature 32 °C, and shaking at 160 rpm/min for 7 days. The production of emodin could achieve 132.40 ± 3.09 mg/L, with no significant difference from the predicted value (132.47 mg/L). Furthermore, KH2PO4 supplementation strategy was employed to regulate the mycelial morphology, upregulate the transcriptional level of biosynthesis gene cluster, and enhance emodin production (185.56 ± 4.39 mg/L).

Artificial exosomes for translational nanomedicine.

Exosomes are lipid bilayer membrane vesicles and are emerging as competent nanocarriers for drug delivery. The clinical translation of exosomes faces many challenges such as massive production, standard isolation, drug loading, stability and quality control. In recent years, artificial exosomes are emerging based on nanobiotechnology to overcome the limitations of natural exosomes. Major types of artificial exosomes include 'nanovesicles (NVs)', 'exosome-mimetic (EM)' and 'hybrid exosomes (HEs)', which are obtained by top-down, bottom-up and biohybrid strategies, respectively. Artificial exosomes are powerful alternatives to natural exosomes for drug delivery. Here, we outline recent advances in artificial exosomes through nanobiotechnology and discuss their strengths, limitations and future perspectives. The development of artificial exosomes holds great values for translational nanomedicine.

From blood to brain: blood cell-based biomimetic drug delivery systems.

Brain drug delivery remains a major difficulty for several challenges including the blood-brain barrier, lesion spot targeting, and stability during circulation. Blood cells including erythrocytes, platelets, and various subpopulations of leukocytes have distinct features such as long-circulation, natural targeting, and chemotaxis. The development of biomimetic drug delivery systems based on blood cells for brain drug delivery is growing fast by using living cells, membrane coating nanotechnology, or cell membrane-derived nanovesicles. Blood cell-based vehicles are superior delivery systems for their engineering feasibility and versatile delivery ability of chemicals, proteins, and all kinds of nanoparticles. Here, we focus on advances of blood cell-based biomimetic carriers for from blood to brain drug delivery and discuss their translational challenges in the future.

[Photosynthetic Parameters Inversion Algorithm Study Based on Chlorophyll Fluorescence Induction Kinetics Curve].

The fast chlorophyll fluorescence induction curve contains rich information of photosynthesis. It can reflect various information of vegetation, such as, the survival status, the pathological condition and the physiology trends under the stress state. Through the acquisition of algae fluorescence and induced optical signal, the fast phase of chlorophyll fluorescence kinetics curve was fitted. Based on least square fitting method, we introduced adaptive minimum error approaching method for fast multivariate nonlinear regression fitting toward chlorophyll fluorescence kinetics curve. We realized Fo (fixedfluorescent), Fm (maximum fluorescence yield), σPSII (PSII functional absorption cross section) details parameters inversion and the photosynthetic parameters inversion of Chlorella pyrenoidosa. And we also studied physiological variation of Chlorella pyrenoidosa under the stress of Cu(2+).