Early change of plasma Epstein-Barr virus DNA load and the viral lytic genome level could positively predict clinical outcome in recurrent or metastatic nasopharyngeal carcinoma receiving anti-programmed cell death 1 monotherapy.

PURPOSE: Patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) have proven benefit from anti-programmed cell death 1 (anti-PD-1) monotherapy. Here, we retrospectively analyze the association of plasma Epstein-Barr virus (EBV) DNA load and tumor viral lytic genome with clinical outcome from 2 registered phase I trials. METHODS: Patients with RM-NPC from Checkmate 077 (nivolumab phase I trial in China) and Camrelizumab phase I trial between March 2016 and January 2018 were enrolled. Baseline EBV DNA titers were tested in 68 patients and EBV assessment was performed in 60 patients who had at least 3 post-baseline timepoints of EBV data and at least 1 post-baseline timepoint of radiographic assessment. We defined "EBV response" as 3 consecutive timepoints of load below 50% of baseline, and "EBV progression" as 3 consecutive timepoints of load above 150% of baseline. Whole-exome sequencing was performed in 60 patients with available tumor samples. RESULTS: We found that the baseline EBV DNA load was positively correlated with tumor size (spearman p < 0.001). Both partial response (PR) and stable disease (SD) patients had significantly lower EBV load than progression disease (PD) patients. EBV assessment was highly consistent with radiographic evaluation. Patients with EBV response had significantly improved overall survival (OS) than patients with EBV progression (log-rank p = 0.004, HR = 0.351 [95% CI: 0.171-0.720], median 22.5 vs. 11.9 months). The median time to initial EBV response and progression were 25 and 36 days prior to initial radiographic response and progression, respectively. Patients with high levels of EBV lytic genomes at baseline, including BKRF2, BKRF3 and BKRF4, had better progression-free survival (PFS) and OS. CONCLUSION: In summary, early clearance of plasma EBV DNA load and high levels of lytic EBV genes were associated with better clinical outcome in patients with RM-NPC receiving anti-PD-1 monotherapy.

Tadpole-Like Carbon Nanotube with Fe Nanoparticle Encapsulated at the Head and Zn Single-Atom Anchored on the Body: One-Pot Carbonization for Tetramodal Synergistic Cancer Therapy.

Precise integration of diverse therapeutic approaches into nanomaterials is the key to the development of multimodal synergistic cancer therapy. In this work, tadpole-like carbon nanotubes with Fe nanoparticle encapsulated at the head and Zn single-atom anchored on the body (Fe@CNT-Zn) is precisely designed and facilely prepared via one-pot carbonization. In vitro studies revealed the integration of chemotherapy (CT), chemodynamic therapy (CDT), photothermal therapy (PTT), and photodynamic therapy (PDT) in Fe@CNT-Zn as well as the near-infrared light (NIR)-responsive cascade therapeutic efficacy. Furthermore, in vivo studies demonstrated the NIR-triggered cascade-amplifying synergistic cancer therapy in a B16 tumor-bearing mouse model. The results not only showcased the Fe@CNT-Zn as a potential tetramodal therapeutic platform, but also demonstrated a proof-of-concept on metal-organic framework-based "one stone for multiple birds" strategy for in situ functionalization of carbon materials.

Suppression of plant immunity by Verticillium dahliae effector Vd6317 through AtNAC53 association.

Verticillium dahliae, a soil-borne fungal pathogen, compromises host innate immunity by secreting a plethora of effectors, thereby facilitating host colonization and causing substantial yield and quality losses. The mechanisms underlying the modulation of cotton immunity by V. dahliae effectors are predominantly unexplored. In this study, we identified that the V. dahliae effector Vd6317 inhibits plant cell death triggered by Vd424Y and enhances PVX viral infection in Nicotiana benthamiana. Attenuation of Vd6317 significantly decreased the virulence of V. dahliae, whereas ectopic expression of Vd6317 in Arabidopsis and cotton enhanced susceptibility to V. dahliae infection, underscoring Vd6317's critical role in pathogenicity. We observed that Vd6317 targeted the Arabidopsis immune regulator AtNAC53, thereby impeding its transcriptional activity on the defense-associated gene AtUGT74E2. Arabidopsis nac53 and ugt74e2 mutants exhibited heightened sensitivity to V. dahliae compared to wild-type plants. A mutation at the conserved residue 193L of Vd6317 abrogated its interaction with AtNAC53 and reduced the virulence of V. dahliae, which was partially attributable to a reduction in Vd6317 protein stability. Our findings unveil a hitherto unrecognized regulatory mechanism by which the V. dahliae effector Vd6317 directly inhibits the plant transcription factor AtNAC53 activity to suppress the expression of AtUGT74E2 and plant defense.

Innervation of nociceptor neurons in the spleen promotes germinal center responses and humoral immunity.

Peripheral sensory neurons widely innervate various tissues to continuously monitor and respond to environmental stimuli. Whether peripheral sensory neurons innervate the spleen and modulate splenic immune response remains poorly defined. Here, we demonstrate that nociceptive sensory nerve fibers extensively innervate the spleen along blood vessels and reach B cell zones. The spleen-innervating nociceptors predominantly originate from left T8-T13 dorsal root ganglia (DRGs), promoting the splenic germinal center (GC) response and humoral immunity. Nociceptors can be activated by antigen-induced accumulation of splenic prostaglandin E2 (PGE2) and then release calcitonin gene-related peptide (CGRP), which further promotes the splenic GC response at the early stage. Mechanistically, CGRP directly acts on B cells through its receptor CALCRL-RAMP1 via the cyclic AMP (cAMP) signaling pathway. Activating nociceptors by ingesting capsaicin enhances the splenic GC response and anti-influenza immunity. Collectively, our study establishes a specific DRG-spleen sensory neural connection that promotes humoral immunity, suggesting a promising approach for improving host defense by targeting the nociceptive nervous system.

Amorphous conversion in pyrolytic symmetric trinuclear nickel clusters trigger trifunctional electrocatalysts.

The pursuit of multifunctional electrocatalysts holds significant importance due to their comprehension of material chemistry. Amorphous materials are particularly appealing, yet they pose challenges in terms of rational design due to their structural disorder and thermal instability. Herein, we propose a strategy that entails the tandem (low-temperature/250-350 °C) pyrolysis of molecular clusters, enabling preservation of the local short-range structures of the precursor Schiff base nickel (Ni3[2(C21H24N3Ni1.5O6)]). The temperature-dependent residuals demonstrate exceptional activity and stability for at least three distinct electrocatalytic processes, including the oxygen evolution reaction (η10 = 197 mV), urea oxidation reaction (η10 = 1.339 V), and methanol oxidation reaction (1358 mA cm-2 at 0.56 V). Three distinct nickel atom motifs are discovered for three efficient electrocatalytic reactions (Ni1 and Ni1' are preferred for UOR/MOR, while Ni2 is preferred for OER). Our discoveries pave the way for the potential development of multifunctional electrocatalysts through disordered engineering in molecular clusters under tandem pyrolysis.

Association between atherogenic index of plasma and depressive symptoms in US adults: Results from the National Health and Nutrition Examination Survey 2005 to 2018.

OBJECTIVE: This study, utilizing data from the U.S. National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018, investigates the association between the atherogenic index of plasma (AIP), a lipid biomarker, and symptoms of depression in American adults. METHODS: In this cross-sectional study of 12,534 adults aged 20 years and older, depressive symptoms were measured utilizing the Patient Health Questionnaire-9 (PHQ-9) scale. Weighted logistic regression models were employed to scrutinize the independent relationship between AIP levels and the likelihood of developing such symptoms. Moreover, a series of subgroup analyses were conducted to delve deeper into these relationships. RESULTS: Following adjustment for confounders, logistic regression by grouping AIP into quartiles revealed a significant association between AIP and an augmented likelihood of self-reported depression. Participants in the fourth quartile (Q4) exhibited a higher odds ratio (OR = 1.34, 95 % CI: 1.02-1.75, p < 0.05) compared to those in the first quartile (Q1). Notably, subgroup analysis unveiled significant interactions involving the smoking and diabetes subgroups, indicating that smoking status and diabetes may modify the relationship between AIP and depression incidence. CONCLUSION: This study reveals a positive correlation between AIP and the self-reported likelihood of depression among US adults, thereby underscoring AIP's potential clinical utility as a biomarker for depressive disorders. Our findings emphasize the necessity to consider and optimize cardiovascular health factors within depression management strategies and offer fresh insights into the development of risk stratification and intervention methods for psychiatric conditions.

METTL14-mediated N6-methyladenosine modification induces the ferroptosis of hypoxia/reoxygenation-induced cardiomyocytes.

BACKGROUND: Hypoxia/reoxygenation (H/R) induces cardiomyocyte ferroptosis, a core remodeling event in myocardial ischemia/reperfusion injury. Methyltransferase-like 14 (METTL14) emerges as a writer of N6-methyladenosine (m6A) modification. This study was conducted to decipher the role of METTL14 in H/R-induced cardiomyocyte ferroptosis. METHODS: Mouse cardiomyocytes HL-1 were cultured and underwent H/R treatment. The degree of ferroptosis after H/R treatment was appraised by the cell counting kit-8 assay, assay kits (ROS/GSH/Fe2+), and Western blotting (GPX4/ACSL4). The intracellular expressions of METTL14, pri-miR-146a-5p, miR-146a-5p, or adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) were examined by real-time quantitative polymerase chain reaction or Western blotting, with m6A quantification analysis and RNA immunoprecipitation to determine the total m6A level and the expression of pri-miR-146a-5p bound to DiGeorge critical region 8 (DGCR8) and m6A-modified pri-miR-146a-5p. The binding of miR-146a-5p to APPL1 was testified by the dual-luciferase assay. RESULTS: H/R treatment induced cardiomyocyte ferroptosis (increased ROS, Fe2+, and ACSL4 and decreased GSH and GPX4) and upregulated METTL14 expression. METTL14 knockdown attenuated H/R-induced cardiomyocyte ferroptosis. METTL14 induced the recognition of pri-miR-146a-5p by DGCR8 by increasing m6A modification on pri-miR-146a-5p, which promoted the conversion of pri-miR-146a-5p into miR-146a-5p and further repressed APPL1 transcription. miR-146a-5p upregulation or APPL1 downregulation limited the inhibitory effect of METTL14 downregulation on H/R-induced cardiomyocyte ferroptosis. CONCLUSION: METTL14 promoted miR-146a-5p expression through the recognition and processing of pri-miR-146a-5p by DGCR8, which repressed APPL1 transcription and triggered H/R-induced cardiomyocyte ferroptosis.

miR-26a-5p inhibits the proliferation of psoriasis-like keratinocytes in vitro and in vivo by dual interference with the CDC6/CCNE1 axis.

Psoriasis is a chronic inflammatory proliferative dermatological ailment that currently lacks a definitive cure. Employing data mining techniques, this study identified a collection of substantially downregulated miRNAs (top 10). Notably, 32 targets were implicated in both the activation of the IL-17 signaling pathway and cell cycle dysregulation. In silico analysis revealed that one of these miRNAs, miR-26a-5p, is a highly conserved cross-species miRNA. Strikingly, the miR-26a-5p sequences in humans and mice are identical, and mmu-miR-26a-5p was found to target the same 7 cell cycle targets as its human counterpart, hsa-miR-26a-5p. Among these targets, CDC6 and CCNE1 were the most effective targets of miR-26a-5p, which was further validated in vitro using a dual luciferase reporter system and qPCR assay. The therapeutic assessment of miR-26a-5p revealed its remarkable efficacy in inhibiting the proliferation and G1/S transition of keratinocytes (HaCaT and HEKs) in vitro. In vivo experiments corroborated these findings, demonstrating that miR-26a-5p effectively suppressed imiquimod (IMQ)-induced psoriasis-like skin lesions in mice over an 8-day treatment period. Histological analysis via H&E staining revealed that miR-26a-5p treatment resulted in reduced keratinocyte thickness and immune cell infiltration into the spleens of IMQ-treated mice. Mechanistic investigations revealed that miR-26a-5p induced a cascade of downregulated genes associated with the IL-23/IL-17A axis, which is known to be critical in psoriasis pathogenesis, while concomitantly suppressing CDC6 and CCNE1 expression. These findings were corroborated by qPCR and Western blot analyses. Collectively, our study provides compelling evidence supporting the therapeutic potential of miR-26a-5p as a safe and reliable endogenous small nucleic acid for the treatment of psoriasis.

Expression and function of VISTA on myeloid cells.

V-domain containing Ig Suppressor of T cell Activation (VISTA) is predominantly expressed on myeloid cells and functions as a ligand/receptor/soluble molecule. In inflammatory responses and immune responses, VISTA regulates multiple functions of myeloid cells, such as chemotaxis, phagocytosis, T cell activation. Since inflammation and immune responses are critical in many diseases, VISTA is a promising therapeutic target. In this review, we will describe the expression and function of VISTA on different myeloid cells, including neutrophils, monocytes, macrophages, dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs). In addition, we will discuss whether the functions of VISTA on these cells impact the disease processing.

A machine learning model identifies M3-like subtype in AML based on PML/RARα targets.

The typical genomic feature of acute myeloid leukemia (AML) M3 subtype is the fusion event of PML/RARα, and ATRA/ATO-based combination therapy is current standard treatment regimen for M3 subtype. Here, a machine-learning model based on expressions of PML/RARα targets was developed to identify M3 patients by analyzing 1228 AML patients. Our model exhibited high accuracy. To enable more non-M3 AML patients to potentially benefit from ATRA/ATO therapy, M3-like patients were further identified. We found that M3-like patients had strong GMP features, including the expression patterns of M3 subtype marker genes, the proportion of myeloid progenitor cells, and deconvolution of AML constituent cell populations. M3-like patients exhibited distinct genomic features, low immune activity and better clinical survival. The initiative identification of patients similar to M3 subtype may help to identify more patients that would benefit from ATO/ATRA treatment and deepen our understanding of the molecular mechanism of AML pathogenesis.

METTL3 promotes cellular senescence of colorectal cancer via modulation of CDKN2B transcription and mRNA stability.

Cellular senescence plays a critical role in cancer development, but the underlying mechanisms remain poorly understood. Our recent study uncovered that replicative senescent colorectal cancer (CRC) cells exhibit increased levels of mRNA N6-methyladenosine (m6A) and methyltransferase METTL3. Knockdown of METTL3 can restore the senescence-associated secretory phenotype (SASP) of CRC cells. Our findings, which were confirmed by m6A-sequencing and functional studies, demonstrate that the cyclin-dependent kinase inhibitor 2B (CDKN2B, encoding p15INK4B) is a mediator of METTL3-regulated CRC senescence. Specifically, m6A modification at position A413 in the coding sequence (CDS) of CDKN2B positively regulates its mRNA stability by recruiting IGF2BP3 and preventing binding with the CCR4-NOT complex. Moreover, increased METTL3 methylates and stabilizes the mRNA of E2F1, which binds to the -208 to -198 regions of the CDKN2B promoter to facilitate transcription. Inhibition of METTL3 or specifically targeting CDKN2B methylation can suppress CRC senescence. Finally, the METTL3/CDKN2B axis-induced senescence can facilitate M2 macrophage polarization and is correlated with aging and CRC progression. The involvement of METTL3/CDKN2B in cell senescence provides a new potential therapeutic target for CRC treatment and expands our understanding of mRNA methylation's role in cellular senescence.

Melatonin as an immunomodulator in CD19-targeting CAR-T cell therapy: managing cytokine release syndrome.

BACKGROUND: Chimeric antigen receptor CAR-T cell therapies have ushered in a new era of treatment for specific blood cancers, offering unparalleled efficacy in cases of treatment resistance or relapse. However, the emergence of cytokine release syndrome (CRS) as a side effect poses a challenge to the widespread application of CAR-T cell therapies. Melatonin, a natural hormone produced by the pineal gland known for its antioxidant and anti-inflammatory properties, has been explored for its potential immunomodulatory effects. Despite this, its specific role in mitigating CAR-T cell-induced CRS remains poorly understood. METHODS: In this study, our aim was to investigate the potential of melatonin as an immunomodulatory agent in the context of CD19-targeting CAR-T cell therapy and its impact on associated side effects. Using a mouse model, we evaluated the effects of melatonin on CAR-T cell-induced CRS and overall survival. Additionally, we assessed whether melatonin administration had any detrimental effects on the antitumor efficacy and persistence of CD19 CAR-T cells. RESULTS: Our findings demonstrate that melatonin effectively mitigated the severity of CAR-T cell-induced CRS in the mouse model, leading to improved overall survival outcomes. Remarkably, melatonin administration did not compromise the antitumor effectiveness or persistence of CD19 CAR-T cells, indicating its compatibility with therapeutic goals. These results suggest melatonin's potential as an immunomodulatory compound to alleviate CRS without compromising the therapeutic benefits of CAR-T cell therapy. CONCLUSION: The study's outcomes shed light on melatonin's promise as a valuable addition to the existing treatment protocols for CAR-T cell therapies. By attenuating CAR-T cell-induced CRS while preserving the therapeutic impact of CAR-T cells, melatonin offers a potential strategy for optimizing and refining the safety and efficacy profile of CAR-T cell therapy. This research contributes to the evolving understanding of how to harness immunomodulatory agents to enhance the clinical application of innovative cancer treatments.

Multiscale Simulations to Discover Self-Assembled Oligopeptides: A Benchmarking Study.

Peptide self-assembly is critical for biomedical and material discovery and production. While it is costly to experimentally test every possible peptide design, computational assessment provides an affordable solution to evaluate many designs and prioritize synthesis and characterization. Following a theoretical investigation, we present a systematic analysis of all-atom and coarse-grained simulations to predict peptide self-assembly. Benchmarking studies of two model dipeptides allow us to assess the impacts of intrinsic properties (such as amino acids and terminal modifications) and external environment (such as salinity) on the simulated aggregation. Further examination of 20 oligopeptides containing two to five amino acids shows good agreement among our theory, simulations, and prior experimental observations. The success rate of our prediction is 90%. Therefore, our theory, simulation, and analysis can be useful to identify peptide designs that can self-assemble and predict the potential nanostructures. These findings lay the ground for future virtual screening of peptide-assembled nanostructures and computer-aided biologics design.

A bibliometric analysis of global research trends of inflammation in cervical cancer: A review.

Cervical cancer is a common malignant tumor and a leading cause of death in women worldwide. It plays a crucial role in tumorigenesis and progression of cervical cancer. A total of 1606 references on inflammation in cervical cancer were retrieved from the Web of Science Core Collection and visual analysis was performed using VOSviewer. Inflammation in cervical cancer has attracted the attention of researchers. Even though China is the country that publishes the most papers, with the most of the top-ranking institutions, there is no extensive collaboration and exchange of papers by Chinese scholars. PLOS One is a popular journal on inflammation in cervical cancer. Instead, authors from other countries perform better, for example, the Sjoerd H. Van Der Burg is the most widely cited author and "M2 macrophages induced by prostaglandin E2 and IL-6 from cervical carcinoma are switched to activated M1 macrophages by CD4 + Th1 cells" (Moniek Heusinkveld, Leiden University Medical Center) is the most cited article of inflammation in cervical cancer. Keywords associated with "apoptosis," "HPV," "NF-κB," and "oxidative stress have been used in many studies, and keywords associated with "apoptosis," "human papillomavirus (HPV)," "NF-κB," and "oxidative stress" are involved in many studies, and there may be more research ideas in the future. From the perspective of precision medicine, more substantive research articles can promote scientific value, strengthen communication and cooperation, produce more extensive research results, and greatly promote the clinical diagnosis and treatment of cervical cancer. All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

CXCL10 and Nrf2-upregulated mesenchymal stem cells reinvigorate T lymphocytes for combating glioblastoma.

BACKGROUND: Lack of tumor-infiltrating T lymphocytes and concurrent T-cell dysfunction have been identified as major contributors to glioblastoma (GBM) immunotherapy resistance. Upregulating CXCL10 in the tumor microenvironment (TME) is a promising immunotherapeutic approach that potentially increases tumor-infiltrating T cells and boosts T-cell activity but is lacking effective delivery methods. METHODS: In this study, mesenchymal stem cells (MSCs) were transduced with a recombinant lentivirus encoding Cxcl10, Nrf2 (an anti-apoptosis gene), and a ferritin heavy chain (Fth) reporter gene in order to increase their CXCL10 secretion, TME survival, and MRI visibility. Using FTH-MRI guidance, these cells were injected into the tumor periphery of orthotopic GL261 and CT2A GBMs in mice. Combination therapy consisting of CXCL10-Nrf2-FTH-MSC transplantation together with immune checkpoint blockade (ICB) was also performed for CT2A GBMs. Thereafter, in vivo and serial MRI, survival analysis, and histology examinations were conducted to assess the treatments' efficacy and mechanism. RESULTS: CXCL10-Nrf2-FTH-MSCs exhibit enhanced T lymphocyte recruitment, oxidative stress tolerance, and iron accumulation. Under in vivo FTH-MRI guidance and monitoring, peritumoral transplantation of CXCL10-Nrf2-FTH-MSCs remarkably inhibited orthotopic GL261 and CT2A tumor growth in C57BL6 mice and prolonged animal survival. While ICB alone demonstrated no therapeutic impact, CXCL10-Nrf2-FTH-MSC transplantation combined with ICB demonstrated an enhanced anticancer effect for CT2A GBMs compared with transplanting it alone. Histology revealed that peritumorally injected CXCL10-Nrf2-FTH-MSCs survived longer in the TME, increased CXCL10 production, and ultimately remodeled the TME by increasing CD8+ T cells, interferon-γ+ cytotoxic T lymphocytes (CTLs), GzmB+ CTLs, and Th1 cells while reducing regulatory T cells (Tregs), exhausted CD8+ and exhausted CD4+ T cells. CONCLUSIONS: MRI-guided peritumoral administration of CXCL10 and Nrf2-overexpressed MSCs can significantly limit GBM growth by revitalizing T lymphocytes within TME. The combination application of CXCL10-Nrf2-FTH-MSC transplantation and ICB therapy presents a potentially effective approach to treating GBM.

Open a new epoch of arsenic trioxide investigation: ATOdb.

Arsenic trioxide (ATO) is a great discovery in the treatment of acute promyelocytic leukemia (APL), which has been used in an increasing number of malignant diseases. Systematic integrative analysis will help to precisely understand the mechanism of ATO and find new combined drugs. Therefore, we developed a one-stop comprehensive database of ATO named ATOdb by manually compiling a wealth of experimentally supported ATO-related data from 3479 articles, and integrated analysis tools. The current version of ATOdb contains 8373 associations among 2300 ATO targets, 80 conditions and 262 combined drugs. Each entry in ATOdb contains detailed information on ATO targets, therapeutic/side effects, systems, cell names, cell types, regulations, detection methods, brief descriptions, references, etc. Furthermore, ATOdb also provides data visualization and analysis results such as the drug similarities, protein-protein interactions, and miRNA-mRNA relationships. An easy-to-use web interface was deployed in ATOdb for users to easily browse, search and download the data. In conclusion, ATOdb will serve as a valuable resource for in-depth study of the mechanism of ATO, discovery of new drug combination strategies, promotion of rational drug use and individualized treatments. ATOdb is freely available at http://bio-bigdata.hrbmu.edu.cn/ATOdb/index.jsp.

Glutaredoxin attenuates glutathione levels via deglutathionylation of Otub1 and subsequent destabilization of system xC.

Glutathione (GSH) is a critical component of the cellular redox system that combats oxidative stress. The glutamate-cystine antiporter, system xC-, is a key player in GSH synthesis that allows for the uptake of cystine, the rate-limiting building block of GSH. It is unclear whether GSH or GSH-dependent protein oxidation [protein S-glutathionylation (PSSG)] regulates the activity of system xC-. We demonstrate that an environment of enhanced PSSG promotes GSH increases via a system xC--dependent mechanism. Absence of the deglutathionylase, glutaredoxin (GLRX), augmented SLC7A11 protein and led to significant increases of GSH content. S-glutathionylation of C23 or C204 of the deubiquitinase OTUB1 promoted interaction with the E2-conjugating enzyme UBCH5A, leading to diminished ubiquitination and proteasomal degradation of SLC7A11 and augmentation of GSH, effects that were reversed by GLRX. These findings demonstrate an intricate link between GLRX and GSH via S-glutathionylation of OTUB1 and system xC- and illuminate a previously unknown feed-forward regulatory mechanism whereby enhanced GSH protein oxidation augments cellular GSH.

Anti-inflammatory effect and mechanism of catalpol in various inflammatory diseases.

Catalpol is a kind of iridoid glucoside, widely found in a variety of plants, mostly extracted from the rhizome of the traditional medicinal herb rehmanniae. It has various biological activities such as anti-inflammatory, antioxidant, and antitumor. The anti-inflammatory effects of catalpol have been demonstrated in a variety of diseases, such as neurological diseases, atherosclerosis, renal diseases, respiratory diseases, digestive diseases, bone and joint diseases, eye diseases, and periodontitis. The purpose of this review is to summarize the existing literature on the anti-inflammatory effects of catalpol in a variety of inflammatory diseases over the last decade and to focus on the anti-inflammatory mechanisms of catalpol.

A global database for modeling tumor-immune cell communication.

Communications between tumor cells and surrounding immune cells help shape the tumor immunity continuum. Recent breakthroughs in high-throughput technologies as well as computational algorithms had reported many important tumor-immune cell (TIC) communications, which were scattered in thousands of published studies and impeded systematical characterization of the TIC communications across cancer. Here, a comprehensive database, TICCom, was developed to model TIC communications, containing 739 experimentally-validated or manually-curated interactions collected from more than 3,000 literatures as well as 4,537,709 predicted interactions inferred via six computational algorithms by reanalyzing 32 scRNA-seq datasets and bulk RNA-seq data across 25 cancer types. The communications between tumor cells and 14 types of immune cells were characterized, and the involved ligand-receptor interactions were further integrated. 14190 human and 3650 mouse integrated ligand-receptor interactions with supplemented corresponding function information were also stored in the TICCom database. Our database would serve as a valuable resource for investigating TIC communications.