Peptide BG From Bitter Gourd () Improves Adjuvant-Induced Arthritis by Modulating the Necroptosis/Neutrophil Extracellular Traps/Inflammation Axis and the Gut Microbiota.

BG is a novel bioactive peptide derived from bitter gourd (), known for its anti-inflammatory and immunomodulatory properties. In the present study, our objective is to investigate the functional roles and mechanisms of BG in the context of rheumatoid arthritis (RA). A rat model of adjuvant-induced arthritis (AIA) was established by administering complete Freund's adjuvant (CFA).

Development and validation of a simple clinical nomogram for predicting infectious diseases in pediatric kidney transplantation recipients: a retrospective study.

To construct and verify an easy-to-use nomogram for predicting the risk of infectious diseases in pediatric kidney transplant recipients. Clinical data of hospitalized pediatric kidney transplant recipients were retrospectively analyzed. Meaningful variables identified from the multivariate stepwise logistic regression analysis were used to construct the nomogram.

The heterogeneity of NOTCH1 to tumor immune infiltration in pan-cancer.

NOTCH1 signaling, a vital regulator of cell proliferation and differentiation, is widely involved in the occurrence and development of malignant tumors. Pharmacological regulation of NOTCH1 is promising in tumor immunotherapy, whereas the effective rate of existing therapies remains low. NOTCH1 functions, as a cancer suppressor or a cancer promoter in different cancers, is engaged in the crosstalk between the immune microenvironment and cancer cells, posing a major challenge to immunotherapy.

Gene Expression Regulation and the Signal Transduction of Programmed Cell Death.

Cell death is of great significance in maintaining tissue homeostasis and bodily functions. With considerable research coming to the fore, it has been found that programmed cell death presents in multiple modalities in the body, which is not only limited to apoptosis, but also can be divided into autophagy, pyroptosis, ferroptosis, mitotic catastrophe, entosis, netosis, and other ways. Different forms of programmed cell death have disparate or analogous characteristics with each other, and their occurrence is accompanied by multiple signal transduction and the role of a myriad of regulatory factors.

Thymic microenvironment's impact on immunosenescence.

Age-related thymic involution is characterized by the loss of T cell development and the supporting epithelial network, which are replaced by adipose tissue. We previously showed that aging functionally impairs lymphohematopoietic progenitor cells, including thymic early T cell progenitors (ETPs), contributing to thymic involution. Considering that the thymic microenvironment is essential for thymocyte incubation, we aimed to investigate its role in age-related thymic involution and the mechanisms underlying these changes.

Identification of RFC4 as a potential biomarker for pan-cancer involving prognosis, tumour immune microenvironment and drugs.

RFC4 is required for DNA polymerase δ and DNA polymerase ε to initiate DNA template expansion. Downregulated RFC4 inhibits tumour proliferation by causing S-phase arrest and inhibiting mitosis, resulting in the reduction of tumour cells. RFC4 has been implicated that it plays an important role in the initiation and progression of cancers, but a comprehensive analysis of the role of RFC4 in cancer has not been performed.

The Role of Oxidative Stress in Tumorigenesis and Progression.

Oxidative stress refers to the imbalance between the production of reactive oxygen species (ROS) and the endogenous antioxidant defense system. Its involvement in cell senescence, apoptosis, and series diseases has been demonstrated. Advances in carcinogenic research have revealed oxidative stress as a pivotal pathophysiological pathway in tumorigenesis and to be involved in lung cancer, glioma, hepatocellular carcinoma, leukemia, and so on.

Identification of specific prognostic markers for lung squamous cell carcinoma based on tumor progression, immune infiltration, and stem index.

Introduction: Lung squamous cell carcinoma (LUSC) is a unique subform of nonsmall cell lung cancer (NSCLC). The lack of specific driver genes as therapeutic targets leads to worse prognoses in patients with LUSC, even with chemotherapy, radiotherapy, or immune checkpoint inhibitors. Furthermore, research on the LUSC-specific prognosis genes is lacking.

UTX inactivation in germinal center B cells promotes the development of multiple myeloma with extramedullary disease.

UTX/KDM6A, a histone H3K27 demethylase and a key component of the COMPASS complex, is frequently lost or mutated in cancer; however, its tumor suppressor function remains largely uncharacterized in multiple myeloma (MM). Here, we show that the conditional deletion of the X-linked Utx in germinal center (GC) derived cells collaborates with the activating Braf mutation and promotes induction of lethal GC/post-GC B cell malignancies with MM-like plasma cell neoplasms being the most frequent. Mice that developed MM-like neoplasms showed expansion of clonal plasma cells in the bone marrow and extramedullary organs, serum M proteins, and anemia.

Comprehensive Analysis of FASN in Tumor Immune Infiltration and Prognostic Value for Immunotherapy and Promoter DNA Methylation.

Fatty acid synthase (FASN) promotes tumor progression in multiple cancers. In this study, we comprehensively examined the expression, prognostic significance, and promoter methylation of FASN, and its correlation with immune cell infiltration in pan-cancer. Our results demonstrated that elevated FASN expression was significantly associated with an unfavorable prognosis in many cancer types.

S100A6 Activates Kupffer Cells via the p-P38 and p-JNK Pathways to Induce Inflammation, Mononuclear/macrophage Infiltration Sterile Liver Injury in Mice.

Noninfectious liver injury, including the effects of chemical material, drugs and diet, is a major cause of liver diseases worldwide. In chemical and drugs-induced liver injury, innate inflammatory responses are mediated by extracellular danger signals. The S100 protein can act as danger signals, which can promote the migration and chemotaxis of immune cells, promote the release of various inflammatory cytokines, and regulate the body's inflammatory and immune responses.

Upregulated miR-322-5p regulates cell cycle and promotes cell proliferation and apoptosis by directly targeting Wee1 in mice liver injury.

Liver injury from any number of causes (e.g. chemical material, drugs and diet, viral infection) is a global health problem, and its mechanism is not clearly understood.

The Traditional Mongolian Medicine Qiqirigan-8 Effects on Lipid Metabolism and Inflammation in Obesity: Pharmacodynamic Evaluation and Relevant Metabolites.

Traditional Mongolian Medicine Qiqirigan-8 (MMQ-8) is a Chinese botanical drug with effective pharmacological properties in obesity. However, the pharmacological mechanism of MMQ-8 remains unclear. This study aimed to determine the active metabolites of MMQ-8 and its therapeutic effects on lipid metabolism and inflammation.

The role of epigenetic modifications in Colorectal Cancer Metastasis.

Distant metastasis is the major contributor to the high mortality rate of colorectal cancer (CRC). To overcome the poor prognosis caused by distant metastasis, the mechanisms of CRC metastasis should be further explored. Epigenetic events are the main mediators of gene regulation and further affect tumor progression.

Traditional Mongolian medicine (HHQG) attenuates CCl-induced acute liver injury through inhibiting monocyte/macrophage infiltration via the p-P38/p-JNK pathway.

Ethnopharmacological Relevance: Honghua Qinggan 13 Flavor Pills (HHQG), whose Mongolian name is Guri Gumu-13, is a traditional Mongolian medicine, that was stated in the "Diagnosis and Treatment of Ming Medical Code". The HHQG has been included in the Mongolian Medicine Division of the Ministry of Health Drug Standards (1998 edition). Based on our clinical expertise, HHQG demonstrated satisfactory therapeutic effects in hepatitis and liver failure.

Liposomes Encapsulating Neoantigens and Black Phosphorus Quantum Dots for Enhancing Photothermal Immunotherapy.

Colorectal cancer frustrates with high relapse after the traditional treatment including surgery and chemotherapy. Neoantigen-based therapeutic vaccine has achieved high response rate in the clinical trials rising the immunotherapy as a promising alternative for colorectal cancer. Herein, colon cancer cells derived neoantigen peptide Adpgk were employed to be co-encapsulated with black phosphorus quantum dots into liposome (Adpgk-BPQDs-liposome) as therapeutic vaccine.

Activin A and BMP4 Signaling Expands Potency of Mouse Embryonic Stem Cells in Serum-Free Media.

Inhibitors of Mek1/2 and Gsk3β, known as 2i, and, together with leukemia inhibitory factor, enhance the derivation of embryonic stem cells (ESCs) and promote ground-state pluripotency (2i/L-ESCs). However, recent reports show that prolonged Mek1/2 suppression impairs developmental potential of ESCs, and is rescued by serum (S/L-ESCs). Here, we show that culturing ESCs in Activin A and BMP4, and in the absence of MEK1/2 inhibitor (ABC/L medium), establishes advanced stem cells derived from ESCs (esASCs).

Ezh2 loss propagates hypermethylation at T cell differentiation-regulating genes to promote leukemic transformation.

Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) is a new pathological entity with poor outcomes in T cell ALL (T-ALL) that is characterized by a high incidence of loss-of-function mutations in polycomb repressive complex 2 (PRC2) genes. We generated a mouse model of ETP-ALL by deleting Ezh2, one of the PRC2 genes, in p53-null hematopoietic cells. The loss of Ezh2 in p53-null hematopoietic cells impeded the differentiation of ETPs and eventually induced ETP-ALL-like disease in mice, indicating that PRC2 functions as a bona fide tumor suppressor in ETPs.

Triptonide inhibits the pathological functions of gastric cancer-associated fibroblasts.

Direct attacks on tumour cells with chemotherapeutic drugs have the drawbacks of accelerating tumour metastasis and inducing tumour stem cell phenotypes. Inhibition of tumour-associated fibroblasts, which provide nourishment and support to tumour cells, is a novel and promising anti-tumour strategy. However, effective drugs against tumour-associated fibroblasts are currently lacking.

Recurrent SPI1 (PU.1) fusions in high-risk pediatric T cell acute lymphoblastic leukemia.

The outcome of treatment-refractory and/or relapsed pediatric T cell acute lymphoblastic leukemia (T-ALL) is extremely poor, and the genetic basis for this is not well understood. Here we report comprehensive profiling of 121 cases of pediatric T-ALL using transcriptome and/or targeted capture sequencing, through which we identified new recurrent gene fusions involving SPI1 (STMN1-SPI1 and TCF7-SPI1). Cases positive for fusions involving SPI1 (encoding PU.

Dual Inhibition of EZH2 and EZH1 Sensitizes PRC2-Dependent Tumors to Proteasome Inhibition.

EZH2 and EZH1, the catalytic components of polycomb repressive complex 2 (PRC2), trigger trimethylation of H3K27 (H3K27me3) to repress the transcription of target genes and are implicated in the pathogenesis of various cancers including multiple myeloma and prostate cancer. Here, we investigated the preclinical effects of UNC1999, a dual inhibitor of EZH2 and EZH1, in combination with proteasome inhibitors on multiple myeloma and prostate cancer. and efficacy of UNC1999 and the combination with proteasome inhibitors was evaluated in multiple myeloma cell lines, primary patient cells, and in a xenograft model.

The loss of Ezh2 drives the pathogenesis of myelofibrosis and sensitizes tumor-initiating cells to bromodomain inhibition.

EZH2 is a component of polycomb repressive complex 2 (PRC2) and functions as an H3K27 methyltransferase. Loss-of-function mutations in EZH2 are associated with poorer outcomes in patients with myeloproliferative neoplasms (MPNs), particularly those with primary myelofibrosis (MF [PMF]). To determine how EZH2 insufficiency is involved in the pathogenesis of PMF, we generated mice compound for an Ezh2 conditional deletion and activating mutation in JAK2 (JAK2V617F) present in patients with PMF.

[Influence of PAX2 gene silencing on renal interstitial fibrosis in rats].

Objective: To investigate the influence of silencing PAX2 gene in vivo on epithelial-mesenchymal transition (EMT) of renal tubular cells in rats with renal interstitial fibrosis.

Methods: A total of 64 Wistar rats were anaesthetized, and unilateral ureteral obstruction (UUO) was performed to establish a rat model of renal interstitial fibrosis. The 64 rats were randomly divided into negative control and PAX2 gene silencing groups (n=32 each).