The causal relationship between genetically predicted blood metabolites and idiopathic pulmonary fibrosis: A bidirectional two-sample Mendelian randomization study.

BACKGROUND: Numerous metabolomic studies have confirmed the pivotal role of metabolic abnormalities in the development of idiopathic pulmonary fibrosis (IPF). Nevertheless, there is a lack of evidence on the causal relationship between circulating metabolites and the risk of IPF. METHODS: The potential causality between 486 blood metabolites and IPF was determined through a bidirectional two-sample Mendelian randomization (TSMR) analysis. A genome-wide association study (GWAS) involving 7,824 participants was performed to analyze metabolite data, and a GWAS meta-analysis involving 6,257 IPF cases and 947,616 control European subjects was conducted to analyze IPF data. The TSMR analysis was performed primarily with the inverse variance weighted model, supplemented by weighted mode, MR-Egger regression, and weighted median estimators. A battery of sensitivity analyses was performed, including horizontal pleiotropy assessment, heterogeneity test, Steiger test, and leave-one-out analysis. Furthermore, replication analysis and meta-analysis were conducted with another GWAS dataset of IPF containing 4,125 IPF cases and 20,464 control subjects. Mediation analyses were used to identify the mediating role of confounders in the effect of metabolites on IPF. RESULTS: There were four metabolites associated with the elevated risk of IPF, namely glucose (odds ratio [OR] = 2.49, 95% confidence interval [95%CI] = 1.13-5.49, P = 0.024), urea (OR = 6.24, 95% CI = 1.77-22.02, P = 0.004), guanosine (OR = 1.57, 95%CI = 1.07-2.30, P = 0.021), and ADpSGEGDFXAEGGGVR (OR = 1.70, 95%CI = 1.00-2.88, P = 0.0496). Of note, the effect of guanosine on IPF was found to be mediated by gastroesophageal reflux disease. Reverse Mendelian randomization analysis displayed that IPF might slightly elevate guanosine levels in the blood. CONCLUSION: Conclusively, hyperglycemia may confer a promoting effect on IPF, highlighting that attention should be paid to the relationship between diabetes and IPF, not solely to the diagnosis of diabetes. Additionally, urea, guanosine, and ADpSGEGDFXAEGGGVR also facilitate the development of IPF. This study may provide a reference for analyzing the potential mechanism of IPF and carry implications for the prevention and treatment of IPF.

Clinical efficacy and potential mechanism of ginseng polysaccharides in the treatment of non-small cell lung cancer based on meta-analysis associated with network pharmacology.

Background: The ginseng polysaccharide injection is a well-known traditional Chinese medicine often employed as a supplementary treatment for cancer. This treatment can not only alleviate the adverse effects caused by tumor radiotherapy and chemotherapy but also enhance the immune system of individuals diagnosed with lung cancer. It is important to acknowledge the efficacy of ginseng polysaccharide injection in the treatment of non-small cell lung cancer (NSCLC). However, these small-sample studies may have certain biases, and the underlying mechanisms of ginseng polysaccharides therapy for NSCLC are still unclear. Methods: The present study involved a systematic review of the literature on randomized controlled trials (RCTs) focusing on using ginseng polysaccharide injection as a therapeutic approach for NSCLC. Seven databases were searched for eligible studies published before April 2023. Two researchers independently managed data extraction, risk of bias assessment, and data analyses using RevMan 5.3 software. In network pharmacology, we thoroughly searched the relevant literature on ginseng polysaccharides (GPs) and the PubChem database. This search aimed to identify the main active ingredients and targets associated with ginseng polysaccharides. Subsequently, we compared these targets with those of NSCLC and utilized bioinformatics techniques to analyze and explore their potential interactions. Results: A total of 11 RCTs involving 845 patients with NSCLC were included in the meta-analysis. The meta-analysis revealed that ginseng polysaccharide injection combined significantly improved the objective response rate [RR = 1.45, 95% CI (1.26, 1.67), P < 0.00001]. Furthermore, it was observed that ginseng polysaccharide injection increased the serum levels of CD4+ T-lymphocytes (CD4+ T) [MD = 8.98, 95% CI (5.18, 12.78), P < 0.00001], and decreased the serum levels of CD8+ T-lymphocytes (CD8+ T) [MD = -2.68, 95% CI (-4.66, -0.70), P = 0.008]. Through network pharmacology analysis, a total of 211 target genes of GPs and 81 common targets were identified. GAPDH, EGFR, VEGFA, JUN, SRC, CASP3, STAT3, CCND1, HSP90AA1, and MMP9 were identified as the core target proteins. Additionally, KEGG enrichment analysis revealed 122 relevant signaling pathways, including Pathways in cancer, PD-L1 expression and PD-1 checkpoint pathway in cancer, and Proteoglycans in cancer. Conclusion: Ginseng polysaccharide injection can improve the ORR of patients with NSCLC, increase the serum levels of CD4+ T, and decrease the serum levels of CD8+ T. The potential mechanism may be associated with the PD-1/PD-L1 signaling pathway.

Dual-channel fluorescent probe for discriminative detection of H2S and N2H4: Exploring sensing mechanism and real-time applications.

A highly efficient system incorporates the real-time visualization of the two toxic molecules (H2S and N2H4) and the recognition of corresponding transforms using a fluorescent sensor. In this paper, a dual-responsive probe (QS-DNP) based on methylquinolinium-salicyaldehyde-2,4-dinitrophenyl was developed that can simultaneously detect H2S and N2H4 at two independent fluorescent channels without signal crosstalk. QS-DNP showed excellent anti-interference, high selectivity, outstanding water solubility, low LOD values (H2S: 51 nM; N2H4: 40 nM), low cytotoxicity, and mitochondrial localization properties. The 2,4-dinitrophenyl site was sensitive to H2S, and the CC bridge was reactive to N2H4, with strong fluorescence at 680 and 488 nm, respectively. The wavelength gap between these two channels is 192 nm; verify that there is no signal crosstalk throughout detection. By this means, the probe was used to simultaneously detect H2S and N2H4 in real soil samples, food samples, and living cells. The endogenous H2S and N2H4 were monitored in HeLa cells and investigated the mitochondria organelle of living cells with a positive charge on QS-DNP. Overall, all results emphasize that the QS-DNP probe is a powerful tool for the simultaneous detection of H2S and N2H4 and presents a potential new sensing approach.

Exploration of Molecular Targets and Mechanisms of Curcumin in the Treatment of COVID-19 with Depression by an Integrative Pharmacology Strategy.

BACKGROUND: Coronavirus disease 2019 (COVID-19) not only causes a range of respiratory symptoms but also has a great impact on individual mental health. With the global pandemic of SARS-CoV-2, the incidence of COVID-19 comorbid with depression has increased significantly. Curcumin, a natural polyphenol compound, has been shown to have antidepressant and anti-coronavirus activities. METHODS: This study aimed to explore the molecular targets and underlying biological mechanisms of curcumin in the treatment of COVID-19 with depression through an integrative pharmacology strategy, including target prediction, network analysis, PPI analysis, GO and KEGG enrichment analyses, and molecular docking. RESULTS: After a comprehensive search and thorough analysis, 8 core targets (ALB, AKT1, CASP3, STAT3, EGFR, PTGS2, FOS, and SERPINE1) were identified. GO and KEGG enrichment analysis results revealed that the pathways related to viral infection, immune regulation, neuronal reorganization, apoptosis, and secretion of inflammatory cytokines were involved in the pathological process. Furthermore, molecular docking showed that curcumin could spontaneously bind to the SARS-CoV-2-related receptor proteins and the core targets with a strong binding force. CONCLUSION: The potential pharmacological mechanisms of curcumin in COVID-19 comorbid depression were evaluated. Curcumin can be used as a therapeutic agent for COVID-19 comorbid depression. One of the potential mechanisms may be to reduce the inflammatory response and suppress the cytokine storm by regulating the JAK-STAT signaling pathway and MAPK signaling pathway. These findings may help to overcome the impact of the COVID-19 pandemic on psychological health.

Effect of Cinobufacini plus platinum-based chemotherapy regimen on the immune function of patients with non-small-cell lung cancer: A meta-analysis.

Background: Cinobufacini is a Chinese medicinal preparation extracted from the traditional Chinese medicine toad skin and is commonly used clinically as an adjuvant treatment for malignant tumours. Purpose: To systematically evaluate the effects of Cinobufacini combined with a first-line platinum-based chemotherapy regimen in patients with non-small-cell lung cancer (NSCLC), especially in terms of immune function. Materials and methods: Eight electronic databases were searched for randomised controlled trials (RCTs) investigating Cinobufacini in conjunction with platinum-based chemotherapy for NSCLC (stage III-IV) published from 2012 to the present. GRADE Pro GDT was used to assess RCT quality and meta-analysis was performed mainly using Review Manager version 5.4, with the assistance of Stata version 16.0 (StataCorp LLC, College Station, TX, USA), and trial sequential analysis software. Results: A total of 35 studies were included. Meta-analysis revealed that the combination therapy group exhibited a better disease control rate (DCR) [OR = 2.63, 95%CI (2.15, 3.21), P < 0.00001], with a higher one-year [OR = 2.41,95% CI (1.75,3.33), P < 0.00001], and two-year [OR = 2.28, 95% CI (1.56,3.33), P < 0.00001] survival rate, plus lower leukocyte toxicity [OR = 0.40, 95%CI (0.33,0.49), P < 0.00001]. For immune function, the combination of chemotherapy with Cinobufacini effectively increased the proportion of CD3+ [SMD = 1.15, 95% CI (0.89,1.42), P < 0.00001], CD4+ [SMD = 1.60, 95%CI (1.26,1.94), P < 0.00001] and the CD4+/CD8+ ratio [SMD = 2.15, 95% CI (1.45,2.86), P < 0.00001] in peripheral blood. Conclusion: The addition of Cinobufacini to platinum-based chemotherapies for advanced NSCLC significantly improved clinical efficacy, enhanced immune function, and reduced chemotherapeutic toxicity, irrespective of administration and treatment duration.

Association of body mass index with mortality of sepsis or septic shock: an updated meta-analysis.

BACKGROUND: The effects of body mass index (BMI) on mortality of sepsis remain unknown, since previous meta-analyses have reported conflicting results. Several observational studies published recently have provided new evidence. Thus, we performed this updated meta-analysis. METHODS: PubMed, Embase, Web of Science, and Cochran Library were searched for articles published before February 10, 2023. Observational studies that assessed the association of BMIs with mortality of sepsis patients aged > 18 years were selected. We excluded studies of which data were unavailable for quantitative synthesis. Odds ratios (OR) with 95% confidence interval (CI) were the effect measure, which were combined using fixed-effect or random-effect models. The Newcastle-Ottawa Scale was applied for quality assessment. Subgroups analyses were conducted according to potential confounders. RESULTS: Fifteen studies (105,159 patients) were included in the overall analysis, which indicated that overweight and obese BMIs were associated with lower mortality (OR: 0.79, 95% CI 0.70-0.88 and OR: 0.74, 95% CI 0.67-0.82, respectively). The association was not significant in patients aged ≤ 50 years (OR: 0.89, 95% CI 0.68-1.14 and OR: 0.77, 95% CI 0.50-1.18, respectively). In addition, the relationship between morbidly obesity and mortality was not significant (OR: 0.91, 95% CI 0.62-1.32). CONCLUSIONS: Overweight and obese BMIs (25.0-39.9 kg/m2) are associated with reduced mortality of patients with sepsis or septic shock, although such survival advantage was not found in all crowds. Trial registration The protocol of this study was registered in PROSPERO (registration number CRD42023399559).

Volumetric absorptive microsampling as an effective microsampling technique for LC-MS/MS bioanalysis of biomarkers in drug discovery.

Aim: Develop and validate a volumetric absorptive microsampling (VAMS)-based LC-MS/MS method to support the bioanalysis of amino acid and carboxylic acid biomarkers in mouse whole blood. Method: Mouse whole blood was collected using a 10 µl VAMS device. The analytes in VAMS were extracted and analyzed using an LC-MS/MS method. Results: The VAMS-based LC-MS/MS assay exhibited a linearity range of 10.0-10,000 ng/ml with acceptable precision and accuracy and consistent recovery. The analyte stability in mouse whole blood VAMS was shown for 7 days at ambient conditions and at -80°C, as well as with three freeze/thaw cycles. Conclusion: A simple and robust VAMS-based LC-MS/MS method was developed and further validated for simultaneous bioanalysis of nine biomarkers in mouse whole blood.

Au Nanozyme Driven Cascading Catalysis in Tollens' Reaction: An Insight of Glucose Oxidase-Like Mechanism.

Au nanoparticles (NPs) have been proven to be excellent glucose oxidase (GOx) mimics, which can catalyze the electrons transform pathway from glucose to oxygen. This study confirmed AuNPs can accelerate the reaction between [Ag(NH3 )2 ]+ and glucose under alkaline conditions, which is also known as the Tollens' reaction, and the possible mechanism was proposed. Here, [Ag(NH3 )2 ]+ instead of O2 acted directedly as an electron acceptor during glucose oxidation catalyzed by AuNPs, accompanied by hydrogen transfer. The as-synthesized Ag nanoparticles can also catalyze this process, similar to AuNPs, via a unique cascading catalysis mechanism in the Tollens' reaction. A simple and heatless glucose colorimetric assay can be established based on the plasmonic band of AgNPs with a liner range of 0.6-22.2 µM, and the limit of detection is 0.32 µM.

A naphthol hydrazone Schiff base bearing benzothiadiazole unit for fluorescent detection of Fe3+ in PC3 cells.

Naphthol hydrazone derivatives are recognized as efficient chelating agents for both qualitative and quantitative detection of metal ions. Here we design a naphthol hydrazine-based chemosensor with covalently linking a strong electron-withdrawing benzothiadiazole group to modulate the molecular electronic structure, nominated as NtHzBtd. The fluorescent probe performs excellent selectivity and sensitivity towards Fe3+ with 1:1 binding stoichiometry, while exhibiting a quick response at 55 s with a relatively low limit of detection of 0.036 µM. A series of spectroscopic measurements in tandem with theoretical calculations suggest that the probe undergoes both intramolecular charge transfer (ICT) and chelation enhanced quenching (CHEQ) processes. Successful color rendering of paper strips and bioimaging in PC3 cells demonstrate the promising applicability of NtHzBtd for portable Fe3+ detection in real samples and biosystems.

Citrullination: A modification important in the pathogenesis of autoimmune diseases.

Peptidyl arginine deiminase (PAD) which mediates citrullination catalyzes the conversion of arginine residues of protein peptide chains to citrulline residues. Citrullination can be involved in the process of apoptosis, embryo development, regulation of myelin sheath function and other physiological processes. Besides, it can regulate the process of cell death, affect the formation of neutrophil extracellular traps (NETs) and produce anti-citrullinated protein antibody (ACPA) to participate in autoimmune diseases. In this manuscript, the regulatory effects of citrullination in normal physiology and autoimmune diseases are reviewed, and the effects of citrullination on immune cells in autoimmune diseases are discussed in detail.

Clinical efficacy and safety of NSCLC ancillary treatment with compound Kushen injection through immunocompetence regulation: A systematic review and meta-analysis.

BACKGROUND: Compound Kushen injection (CKI) is a Chinese patented medicine that improves the immunity level of cancer patients and inhibits tumor cell proliferation and metastasis. Clinically, CKI is widely used in combination with platinum-based chemotherapy (PBC) for non-small cell lung cancer (NSCLC) treatment. This study attempted to systemically evaluate the efficacy and safety of a combination of CKI and PBC for NSCLC treatment by modulating the immune function. PURPOSE: To evaluate the clinical efficacy and safety of CKI in combination with PBC for NSCLC. MATERIALS AND METHODS: English and Chinese databases were retrieved for randomized controlled trials (RCTs) of NSCLC treatment using a combination of CKI and PBC, and the changes of peripheral blood T lymphocytes (such as CD3+ T cells, CD4+ T cells, CD8+ T cells), and CD4+/CD8+ T cell ratio among NSCLC patients were detected before and after treatment using CKI with PBC. The search deadline was set as November 2021. The systemic evaluation was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The methodology and quality of each study included in the systemic evaluation were assessed. Review Manager 5.4, Stata12.0, and trial sequential analysis (TSA) were used for data analysis. The outcome indicators were qualified using GRADEprofiler software. RESULTS: A total of 25 RCTs involving 2460 cases of patients were included. The results showed that the combination of CKI with PBC effectively increased the objective response rate (ORR) [relative risk (RR) = 1.31, 95% confidence interval (CI) (1.19, 1.44)] and disease control rate (DCR) [RR = 1.16, 95%CI (1.09,1.23)], regulated the expression of peripheral blood T lymphocytes (such as CD3+T cells, CD4+T cells, CD8+T cells, and CD4+/CD8+T cell ratio), upregulated the level of serum immunoglobulins (such as IgA, IgG, and IgM), and reduced the frequency of gastrointestinal reaction, marrow inhibition, hepatorenal toxicity, reduction of white blood cells and blood platelets, baldness, infection, neutrophilic granulocyte counts, diarrhea, or constipation. According to subgroup analysis results, chemotherapy cycles (1-2) had a more significant effect on DCR. A combination of CKI and GP regimens had better effects on improving CD3+T cell levels, and there were no significant changes among other chemotherapies regiments. CONCLUSION: A combination of CKI and PBC had a marked effect in improving tumor response, priming immune function, and decreasing the frequency of adverse reactions, which was safe for NSCLC treatment.

Turn-off detection of Cr(III) with chelation enhanced fluorescence quenching effect by a naphthyl hydrazone Shiff base chemosensor.

A thiophene substituted naphthyl hydrazone derivative NHT was synthesized using a one-step route for the detection of trivalent chromium (Cr3+). UV-visible absorption and emission spectra, density functional theory calculations as well as 1H NMR titration confirmed that the probe underwent a turn-off response via the chelation enhanced fluorescence quenching effect upon exposure to Cr3+ and the NHT-Cr3+ complex was formed at a 1:1 binding stoichiometry. NHT exhibited a fast response rate of 2.3 min in buffer solution and a relatively low limit of detection of 41 nM. In addition, the Schiff base chemosensor exhibited excellent selectivity with high affinity towards Cr3+ in the presence of other competing cations. Bioimaging of the probe in PC3 cells further demonstrated the potential real life application of the probe in detecting Cr3+.

Effect of kangai injection combined with platinum-based chemotherapy on the immune function of patients with advanced non-small-cell lung cancer: A meta-analysis.

BACKGROUND: Kangai injection (KAI) is a well-known Chinese patent medicine applied for several different types of cancers in the clinic as an auxiliary therapeutic approach, which is refined from three herbal extracts (Astragalus, Ginseng and Matrine). PURPOSE: To systematically evaluate the effect of combination treatment of platinum-based chemotherapy and KAI on patients with advanced non-small-cell lung cancer (NSCLC). STUDY DESIGN: A meta-analysis of randomized clinical trials. MATERIALS AND METHODS: The randomized controlled trials (RCTs) about stage Ⅲ-Ⅳ NSCLC using KAI combined platinum-based chemotherapy were electronically retrieved from eight electronic databases up to July 2021. We applied RevMan 5.4, Stata 16.0, TSA 0.9.5.10 Beta and GRADE Pro-GDT to evaluate the quality of the included RCTs and perform the meta-analysis. RESULTS: 19 RCTs were included, consisting a total sample size of 1,389 cases. Meta-analysis revealed that compared with chemotherapy alone, KAI combined with platinum-based chemotherapy was associated with significantly higher objective response rate (ORR) [RR = 1.36, 95%CI (1.21,1.54), p< 0.00001], higher disease control rate (DCR) [RR = 1.15, 95%CI (1.09,1.21), p< 0.00001], greater Karnofsky performance status (KPS) [RR = 1.75, 95%CI (1.41,2.18), p< 0.00001], lower white blood cell toxicity [RR = 0.67, 95%CI (0.55,0.82), p = 0.0001], lower platelet toxicity [RR = 0.60, 95%CI (0.47,0.75), P  < 0.0001], and lower incidence of vomiting [RR = 0.66, 95%CI (0.57,0.76), p< 0.00001]. In terms of the immune function, KAI united with chemotherapy significantly raised the ratio of CD3+ cells [MD = 10.65, 95%CI (8.21,13.09), p< 0.00001], CD4+ cells [MD = 7.67, 95%CI (6.31,9.03), p< 0.00001], NK cells [MD = 4.97, 95%CI (3.03,6.92), p< 0.00001], and CD4+/ CD8+ [MD = 0.32, 95%CI (0.19,0.45), p< 0.00001], and decreased the percentage of CD8+ cells [MD = -5.56, 95%CI (-7.51,-3.61), p< 0.00001]. CONCLUSIONS: This meta-analysis identified that the combination treatment of KAI and platinum-based chemotherapy was more beneficial to patients with advanced NSCLC when compared to chemotherapy alone, which could significantly improve the clinical efficacy, enhance the immune function, and reduce chemotherapy toxicity. Our study provides a theoretical basis and treatment guidance for patients with NSCLC.

A simple quinoline-thiophene Schiff base turn-off chemosensor for Hg2+ detection: spectroscopy, sensing properties and applications.

A new Schiff base probe (QT) consisting of 8-aminoquinoline (Q) and thiophene-2-carboxaldehyde (T) moieties has been synthesized. QT undergoes chelation-enhanced fluorescence quenching when exposed to Hg2+ due to coordination by the sulfur and nitrogen atoms of QT thus forming a facile "turn-off" sensor. The formation of the chelation complex was confirmed by UV-visible absorption and emission spectral measurements, 1H NMR titration and density functional theory calculations. These studies revealed that the probe exhibits high selectivity and sensitivity towards Hg2+ in the presence of other common metal ions. A low detection limit of 23.4 nM was determined and a Job plot confirmed a 2:1 stoichiometry between QT and Hg2+. The potential utility of QT as a sensor for Hg2+ ions in human HeLa cells was determined by confocal fluorescence microscopy, and its suitability for use in the field with environmental samples was tested with Whatman filter paper strips.

Quantitative Hg2+ detection via forming three coordination complexes using a lysosome targeting quinoline - Fisher aldehyde fluorophore.

This work describes (Z)-N-((Z)-2-(1,3,3-trimethylindolin-2ylidene)ethylidene)quinoline-8-amine (LYSO-QF), a high-performing and biocompatible dye comprised of quinoline and Fisher aldehyde moieties linked via an imine vinyl backbone with lysosome targeting ability that can be used to quantitatively detect the mercury ion (Hg2+) in biosystems and the natural environment. This is achieved by forming three different tetrameric, trimeric and dimeric complexes between Hg2+ and LYSO-QF with the limit of detection (LOD) of 11 nm. The complexes formed were analyzed with the aid of time-dependent density functional theory (TD-DFT) calculations. The concentration dependence of the Hg2+ complex fluorescence emission changes from grey-green to jade green and then to red as the different types of complex are formed. The favorable sensor properties of the LYSO-QF probe are demonstrated by monitoring different Hg2+ concentrations in buffer solutions, HeLa cells, zebrafish model samples and several different types of water sample. Experiments with Whatman paper strips demonstrate that the cost-effective LYSO-QF also has considerable potential for use in on-site Hg2+ detection with the naked eye.

Histone citrullination: a new target for tumors.

As the main protein components of chromatin, histones play central roles in gene regulation as spools of winding DNA. Histones are subject to various modifications, including phosphorylation, acetylation, glycosylation, methylation, ubiquitination and citrullination, which affect gene transcription. Histone citrullination, a posttranscriptional modification catalyzed by peptidyl arginine deiminase (PAD) enzymes, is involved in human carcinogenesis. In this study, we highlighted the functions of histone citrullination in physiological regulation and tumors. Additionally, because histone citrullination involves forming neutrophil extracellular traps (NETs), the relationship between NETs and tumors was illustrated. Finally, the clinical application of histone citrullination and PAD inhibitors was discussed.

Goose parvovirus and the protein NS1 induce apoptosis through the AIF-mitochondrial pathway in goose embryo fibroblasts.

In this study, the effects of Goose parvovirus (GPV) infection as well as the possible role of NS1 protein on apoptosis induction in goose embryo fibroblast (GEF) cells were examined. Flow cytometry analysis and TUNEL assays revealed that GPV infection and NS1 transfection induced significant apoptosis in GEF cells compared to what was observed in mock-infected cells. Interestingly, the increase in the rate of apoptosis detected in GPV-infected GEFs was accompanied by an increased viral load in the cells. In addition, the apoptotic pathway was mediated by apoptosis-inducing factors (AIFs) and internal factors that influence the release of AIFs. The results indicated that the mitochondrial membrane potential was decreased, and AIF expression was increased in the nucleus (P < 0.01). Reactive oxygen species (ROS) increased gradually within 48 h (P < 0.001). Cathepsin D activities were also increased (P < 0.05). The results demonstrated that the AIF-mediated pathway is a new mitochondrial apoptotic pathway and that mitochondrial depolarization, ROS content, and cathepsin D activities are the key factors influencing apoptosis in GEF cells.

Successive Detection of Zinc Ion and Citrate Using a Schiff Base Chemosensor for Enhanced Prostate Cancer Diagnosis in Biosystems.

Sensitive and quantitative detection of prostate cancer (PC) requires a chemosensor with an applicable sensing strategy. A star-shaped Schiff base triaminoguanidine-integrated thiophene fluorophore TAT was rationally designed with nitrogen and sulfur atoms to coordinate with Zn2+ as the initial step and to chelate with citrate as the following step. Formation of the complex TAT-Zn2+ induced an intramolecular charge transfer and caused a red-shifted, Zn2+ concentration-dependent fluorescence at 507 nm. Chelation of TAT-Zn2+ with citrate led to an emission band at 692 nm upon an aggregation-induced emission mechanism. The distinctive fluorescence emissions of Zn2+ and citrate biomarkers were demonstrated first in on-site paper-based test strips showing gradually enhanced colors at yellow and red channels and second in both in vitro and in vivo by using PC3 cells and BALB/c nude mouse animal models, respectively. The in vitro test confirmed the mitochondria organelle-targeting property of TAT, and the in vivo performance manifested the successful application of the probe in recognizing the prostate cancer. This is the first applicable chemosensor that could be in continuous recognition of dual PC biomarkers Zn2+ and citrate in cancer diagnosis with a mitochondria organelle-targeting ability.

Cognitive Computing-Based CDSS in Medical Practice.

Importance. The last decade has witnessed the advances of cognitive computing technologies that learn at scale and reason with purpose in medicine studies. From the diagnosis of diseases till the generation of treatment plans, cognitive computing encompasses both data-driven and knowledge-driven machine intelligence to assist health care roles in clinical decision-making. This review provides a comprehensive perspective from both research and industrial efforts on cognitive computing-based CDSS over the last decade.Highlights. (1) A holistic review of both research papers and industrial practice about cognitive computing-based CDSS is conducted to identify the necessity and the characteristics as well as the general framework of constructing the system. (2) Several of the typical applications of cognitive computing-based CDSS as well as the existing systems in real medical practice are introduced in detail under the general framework. (3) The limitations of the current cognitive computing-based CDSS is discussed that sheds light on the future work in this direction.Conclusion. Different from medical content providers, cognitive computing-based CDSS provides probabilistic clinical decision support by automatically learning and inferencing from medical big data. The characteristics of managing multimodal data and computerizing medical knowledge distinguish cognitive computing-based CDSS from other categories. Given the current status of primary health care like high diagnostic error rate and shortage of medical resources, it is time to introduce cognitive computing-based CDSS to the medical community which is supposed to be more open-minded and embrace the convenience and low cost but high efficiency brought by cognitive computing-based CDSS.

Granulocytic Myeloid-Derived Suppressor Cell Exosomal Prostaglandin E2 Ameliorates Collagen-Induced Arthritis by Enhancing IL-10+ B Cells.

The results of recent studies have shown that granulocytic-myeloid derived suppressor cells (G-MDSCs) can secrete exosomes that transport various biologically active molecules with regulatory effects on immune cells. However, their roles in autoimmune diseases such as rheumatoid arthritis remain to be further elucidated. In the present study, we investigated the influence of exosomes from G-MDSCs on the humoral immune response in murine collagen-induced arthritis (CIA). G-MDSCs exosomes-treated mice showed lower arthritis index values and decreased inflammatory cell infiltration. Treatment with G-MDSCs exosomes promoted splenic B cells to secrete IL-10 both in vivo and in vitro. In addition, a decrease in the proportion of plasma cells and follicular helper T cells was observed in drainage lymph nodes from G-MDSCs exosomes-treated mice. Moreover, lower serum levels of IgG were detected in G-MDSCs exosomes-treated mice, indicating an alteration of the humoral environment. Mechanistic studies showed that exosomal prostaglandin E2 (PGE2) produced by G-MDSCs upregulated the phosphorylation levels of GSK-3ß and CREB, which play a key role in the production of IL-10+ B cells. Taken together, our findings demonstrated that G-MDSC exosomal PGE2 attenuates CIA in mice by promoting the generation of IL-10+ Breg cells.