The prognostic value of CD8+ CTLs, CD163+ TAMs, and PDL1 expression in the tumor microenvironment of primary central nervous system lymphoma.

To explore immune cell infiltration and PDL1 expression in the tumor microenvironment (TME) of primary central nervous system lymphoma (PCNSL), we performed immunohistochemical staining on paraffin-embedded tumor tissues from 34 patients diagnosed with PCNSL. CD8 and CD163 positive cells were manually counted, and PDL1 expression was quantified by the H-score scoring method in the tumor center and around the tumor. The Kaplan-Meier method was used to analyze the prognostic value of the TME. We found obvious infiltration of CD8+ CTLs and CD163+ TAMs in the TME of PCNSL patients. And PDL1 was expressed in the tumor center as well as around the tumor. Survival analysis showed that high CD8+ CTLs levels and high intratumoral PDL1 expression were significantly correlated with longer OS. High CD8+ CTLs and CD163+ TAMs levels were associated with longer PFS.

Therapeutic potential of gene therapy for gastrointestinal diseases: Advancements and future perspectives.

Advancements in understanding the pathogenesis mechanisms underlying gastrointestinal diseases, encompassing inflammatory bowel disease, gastrointestinal cancer, and gastroesophageal reflux disease, have led to the identification of numerous novel therapeutic targets. These discoveries have opened up exciting possibilities for developing gene therapy strategies to treat gastrointestinal diseases. These strategies include gene replacement, gene enhancement, gene overexpression, gene function blocking, and transgenic somatic cell transplantation. In this review, we introduce the important gene therapy targets and targeted delivery systems within the field of gastroenterology. Furthermore, we provide a comprehensive overview of recent progress in gene therapy related to gastrointestinal disorders and shed light on the application of innovative gene-editing technologies in treating these conditions. These developments are fueling a revolution in the management of gastrointestinal diseases. Ultimately, we discuss the current challenges (particularly regarding safety, oral efficacy, and cost) and explore potential future directions for implementing gene therapy in the clinical settings for gastrointestinal diseases.

Edible exosome-like nanoparticles from portulaca oleracea L mitigate DSS-induced colitis via facilitating double-positive CD4+CD8+T cells expansion.

Plant-derived exosome-like nanoparticles (PDENs) have been paid great attention in the treatment of ulcerative colitis (UC). As a proof of concept, we isolated and identified Portulaca oleracea L-derived exosome-like nanoparticles (PELNs) from edible Portulaca oleracea L, which exhibited desirable nano-size (~ 160 nm) and a negative zeta potential value (-31.4 mV). Oral administration of PELNs effectively suppressed the expressions of pro-inflammatory cytokines (TNF-α, IL-6, IL-12, and IL-1ß) and myeloperoxidase (MPO), increased levels of the anti-inflammatory cytokine (IL-10), and alleviated acute colitis in dextran sulfate sodium (DSS)-induced C57 mice and IL-10-/- mice. Notably, PELNs exhibited excellent stability and safety within the gastrointestinal tract and displayed specific targeting to inflamed sites in the colons of mice. Mechanistically, oral administration of PELNs played a crucial role in maintaining the diversity and balance of gut microbiota. Furthermore, PELNs treatment enhanced Lactobacillus reuteri growth and elevated indole derivative levels, which might activate the aryl-hydrocarbon receptor (AhR) in conventional CD4+ T cells. This activation downregulated Zbtb7b expression, leading to the reprogramming of conventional CD4+ T cells into double-positive CD4+CD8+T cells (DP CD4+CD8+ T cells). In conclusion, our findings highlighted the potential of orally administered PELNs as a novel, natural, and colon-targeted agent, offering a promising therapeutic approach for managing UC. Schematic illustration of therapeutic effects of oral Portulaca oleracea L -derived natural exosome-like nanoparticles (PELNs) on UC. PELNs treatment enhanced Lactobacillus reuteri growth and elevated indole derivative levels, which activate the aryl-hydrocarbon receptor (AhR) in conventional CD4+ T cells leading to downregulate the expression of Zbtb7b, reprogram of conventional CD4+ T cells into double-positive CD4+CD8+T cells (DP CD4+CD8+ T cells), and decrease the levels of pro-inflammatory cytokines.

Application of Nanoparticles in the Diagnosis of Gastrointestinal Diseases: A Complete Future Perspective.

The diagnosis of gastrointestinal (GI) diseases currently relies primarily on invasive procedures like digestive endoscopy. However, these procedures can cause discomfort, respiratory issues, and bacterial infections in patients, both during and after the examination. In recent years, nanomedicine has emerged as a promising field, providing significant advancements in diagnostic techniques. Nanoprobes, in particular, offer distinct advantages, such as high specificity and sensitivity in detecting GI diseases. Integration of nanoprobes with advanced imaging techniques, such as nuclear magnetic resonance, optical fluorescence imaging, tomography, and optical correlation tomography, has significantly enhanced the detection capabilities for GI tumors and inflammatory bowel disease (IBD). This synergy enables early diagnosis and precise staging of GI disorders. Among the nanoparticles investigated for clinical applications, superparamagnetic iron oxide, quantum dots, single carbon nanotubes, and nanocages have emerged as extensively studied and utilized agents. This review aimed to provide insights into the potential applications of nanoparticles in modern imaging techniques, with a specific focus on their role in facilitating early and specific diagnosis of a range of GI disorders, including IBD and colorectal cancer (CRC). Additionally, we discussed the challenges associated with the implementation of nanotechnology-based GI diagnostics and explored future prospects for translation in this promising field.

Exploring the efficacy of herbal medicinal products as oral therapy for inflammatory bowel disease.

Inflammatory bowel disease (IBD) encompasses a collection of idiopathic diseases characterized by chronic inflammation in the gastrointestinal (GI) tract. Patients diagnosed with IBD often experience necessitate long-term pharmacological interventions. Among the multitude of administration routes available for treating IBD, oral administration has gained significant popularity owing to its convenience and widespread utilization. In recent years, there has been extensive evaluation of the efficacy of orally administered herbal medicinal products and their extracts as a means of treating IBD. Consequently, substantial evidence has emerged, supporting their effectiveness in IBD treatment. This review aimed to provide a comprehensive summary of recent studies evaluating the effects of herbal medicinal products in the treatment of IBD. We delved into the regulatory role of these products in modulating immunity and maintaining the integrity of the intestinal epithelial barrier. Additionally, we examined their impact on antioxidant activity, anti-inflammatory properties, and the modulation of intestinal flora. By exploring these aspects, we aimed to emphasize the significant advantages associated with the use of oral herbal medicinal products in the treatment of IBD. Of particular note, this review introduced the concept of herbal plant-derived exosome-like nanoparticles (PDENs) as the active ingredient in herbal medicinal products for the treatment of IBD. The inclusion of PDENs offers distinct advantages, including enhanced tissue penetration and improved physical and chemical stability. These unique attributes not only demonstrate the potential of PDENs but also pave the way for the modernization of herbal medicinal products in IBD treatment.

Stem cell-derived intestinal organoids: a novel modality for IBD.

The organoids represent one of the greatest revolutions in the biomedical field in the past decade. This three-dimensional (3D) micro-organ cultured in vitro has a structure highly similar to that of the tissue and organ. Using the regeneration ability of stem cells, a 3D organ-like structure called intestinal organoids is established, which can mimic the characteristics of real intestinal organs, including morphology, function, and personalized response to specific stimuli. Here, we discuss current stem cell-based organ-like 3D intestinal models, including understanding the molecular pathophysiology, high-throughput screening drugs, drug efficacy testing, toxicological evaluation, and organ-based regeneration of inflammatory bowel disease (IBD). We summarize the advances and limitations of the state-of-the-art reconstruction platforms for intestinal organoids. The challenges, advantages, and prospects of intestinal organs as an in vitro model system for precision medicine are also discussed. Key applications of stem cell-derived intestinal organoids. Intestinal organoids can be used to model infectious diseases, develop new treatments, drug screens, precision medicine, and regenerative medicine.

Colorimetric assay for tetracyclines based on europium ion-induced aggregation of gold nanoparticles.

Oxytetracycline-capped gold nanoparticles (OTC-Au NPs) were prepared using sodium borohydride as the reductant and OTC as the capping agent, respectively. The prepared OTC-Au NPs with a size of 6 nm have a maximum surface plasma resonance (SPR) absorption located at 514 nm. The OTC on the surface of Au NPs still can coordinate with Eu3+ ions. Due to the property that OTC has multivalent binding sites with Eu3+ ions, Eu3+ ions can induce the aggregation of OTC-Au NPs. Based on the Eu3+ ions-aggregated OTC-Au NPs, a simple aptamer-free colorimetric sensing method for TCs was developed. Briefly, free TCs compete with OTC on the surface of Au NPs resulting in the change of OTC-Au NPs from an aggregation state to a dispersed state. The whole process takes only 5 min, and as low as 20 nM OTC, 14 nM tetracycline (TC), and 20 nM doxycycline (DC) could be sensitively detected, respectively. The proposed method was also featured as good repeatability and specificity, and was applied to the detection of OTC in lake water with satisfactory recovery.

A Simple Colorimetric Analytical Assay for the Determination of Tetracyclines Based on In-situ Generation of Gold Nanoparticles Coupling with a Gold Staining Technique.

The development of simple and sensitive detection methods for tetracyclines (TCs) is crucial for their routine detection. The present study developed a colorimetric method for the detection of TCs based on the in-situ generation of AuNPs, which were subsequently coupled with a gold staining reaction. Briefly, TCs containing phenolic groups reduce HAuCl4 to form gold nanoparticles (AuNPs) as gold seeds. In the gold staining process, the gold seeds catalyze the reduction of HAuCl4 by NH2OH to form gold atoms that deposit on the surface of AuNPs, resulting in the enlargement of AuNPs. Sensitive detection of TCs was achieved by employing the gold staining technique. As low as 14, 18.9, and 1.98 nM of oxytetracycline (OTC), tetracycline (TC), and doxycycline (DC), respectively, could be sensitively detected. The proposed method also exhibited good repeatability and specificity, and then was applied to the determination of OTC in milk samples.

Tyrosine-EDC Conjugation, an Undesirable Side Effect of the EDC-Catalyzed Carboxyl Labeling Approach.

Carbodiimide-catalyzed carboxyl and amine conjugation (amidation) has been widely used to protect carboxyl groups. N-(3-(Dimethylamino)propyl)-N'-ethylcarbodiimide (EDC) is the most common carbodiimide reagent in protein chemistry due to its high catalytic efficiency in aqueous media. The reaction has also been applied in different proteomic studies including protein terminomics, glycosylation, and interaction. Herein, we report that the EDC-catalyzed amidation could cause a +155 Da side modification on the tyrosine residue and severely hamper the identification of Tyr-containing peptides. We revealed the extremely low identification rate of Tyr-containing peptides in different published studies employing the EDC-catalyzed amidation. We discovered a +155 Da side modification occurring specifically on Tyr and decoded it as the addition of EDC. Consideration of the side modification in a database search enabled the identification of 13 times more Tyr-containing peptides. Furthermore, we successfully developed an efficient method to remove the side modification. Our results also imply that chemical reactions in proteomic studies should be carefully evaluated prior to their wide applications. Data are available via ProteomeXchange with identifier PXD020042.

Nanomaterial-enhanced chemiluminescence reactions and their applications.

Chemiluminescence (CL) analysis is a trace analytical method that possesses advantages including high sensitivity, wide linear range, easy operation, and simple instruments. With the development of nanotechnology, many nanomaterial (NM)-enhanced CL systems have been established in recent years and applied for the CL detection of metal ions, anions, small molecules, tumor markers, sequence-specific DNA, and RNA. This review summarizes the research progress of the nanomaterial-enhanced CL systems the past five years. These CL reactions include luminol, peroxyoxalate, lucigenin, ultraweak CL reactions, and so on. The CL mechanisms of the nanomaterial-enhanced CL systems are discussed in the first section. Nanomaterials take part in the CL reactions as the catalyst, CL emitter, energy acceptor, and reductant. Their applications are summarized in the second section. Finally, the challenges and opportunities are discussed.

Cationic liposome-triggered luminol chemiluminescence reaction and its applications.

Liposomes are spherical phospholipid bilayer vesicles. In the present study, we found that cationic liposomes made by (2,3-dioleoyloxy-propyl)-trimethylammonium (DOTAP) could enhance the luminol-H2O2 chemiluminescence (CL) reaction. Mechanism studies showed that the positive charge on the surface of liposomes plays an important role in the CL process. We speculated that the cationic liposomes with quaternary ammonium groups on the surface may be capable of catalyzing the decomposition of H2O2 leading to the formation of oxygen-related free radicals including ˙OH, 1O2, and O2˙-. The luminol anions tend to move close to the surface of the cationic liposomes and then to be oxidized by the oxidizing radical species which may be around the surface of cationic liposomes forming excited-state 3-aminophthalate* (3-APA*). When the 3-APA* returns to the ground state, an enhanced CL is observed. In addition, the single-strand DNA (ssDNA) showed a significant inhibition effect on the proposed CL reaction. The CL intensity decreased linearly with an increasing amount of DNA from 0.05 to 2 pmol. We assumed that the binding of ssDNA with cationic liposomes would neutralize the positive charge on the surface of liposomes and inhibit the catalytic activity of DOTAP cationic liposomes. Based on the ssDNA-inhibited luminol-H2O2-cationic liposome CL reaction, simple label-free CL sensing platforms were developed for the detection of sequence-specific DNA related to the hepatitis B virus (HBV) gene and for the detection of ATP (as a model analyte) using an anti-ATP aptamer as the recognition element.

Kobuvirus VP3 protein restricts the IFN-ß-triggered signaling pathway by inhibiting STAT2-IRF9 and STAT2-STAT2 complex formation.

Emerged porcine kobuvirus (PKV) has adversely affected the global swine industry since 2008, but the etiological biology of PKV is unclear. Screening PKV-encoded structural and non-structural proteins with a type I IFN-responsive luciferase reporter showed that PKV VP3 protein inhibited the IFN-ß-triggered signaling pathway, resulting in the decrease of VSV-GFP replication. QPCR data showed that IFN-ß downstream cytokine genes were suppressed without cell-type specificity as well. The results from biochemical experiments indicated that PKV VP3 associated with STAT2 and IRF9, and interfered with the formation of the STAT2-IRF9 and STAT2-STAT2 complex, impairing nuclear translocation of STAT2 and IRF9. Taken together, these data reveal a new mechanism for immune evasion of PKV.

Determination of berberine and the study of fluorescence quenching mechanism between berberine and enzyme-catalyzed product.

A new method for determining berberine has been established based on the principle of fluorescence quenching. The calibration curve was found to be linear between F(0)/F and the concentration of berberine with the range of 3.00-20.0 microg mL(-1). The detection limit was 0.51 microg mL(-1) and the relative standard derivative was 0.18%. Effects of pH, foreign ions and the optimization of variables on the determination of berberine have been examined. The mechanism of the fluorescence quenching has been discussed. The binding constant and the number of binding sites were 1.70x10(6) L mol(-1) and 1.14, respectively. The data, DeltaH = 42.71 kJ mol(-1), DeltaS = 264.3 J K(-1) mol(-1) and the mean value DeltaG = -39.65 kJ mol(-1) were estimated which showed that the reaction was spontaneous and endothermic. The main binding force was hydrophobic force because both DeltaH and DeltaS were positive.

Study of fluorescence quenching mechanism between quercetin and tyrosine-H(2)O(2)-enzyme catalyzed product.

Because of catalysis of horseradish peroxidase, the tyrosine reacted with H(2)O(2) to form the product S which was a strong fluorescence substance. To the product S, the quercetin was acted as a quencher. The fluorescence quenching mechanism was studied by the measurement of fluorescence lifetime and based on the Stern-Volmer plot. The reaction mechanism, which was the static quenching process between quercetin and product S, was studied. The binding constant, K=4.03 x 10(5) L mol(-1) and the number of binding sites n=1.09, were obtained against this reaction. The thermodynamic parameters were estimated. The data, DeltaH=-75.68 kJ mol(-1), DeltaS=-147.9JK(-1) mol(-1) and DeltaG=-29.17 kJ mol(-1) showed that the reaction was spontaneous and exothermic. What is more, both DeltaH and DeltaS were negative values indicated that van der Waals interaction and hydrogen bonding were the predominant intermolecular forces between quercetin and product S.