The molar dose of FAPI administered impacts on the FAP-targeted PET imaging and therapy in mouse syngeneic tumor models.

Purpose: Since fibroblast activation protein (FAP), one predominant biomarker of cancer associated fibroblasts (CAFs), is highly expressed in the tumor stroma of various epidermal-derived cancers, targeting FAP for tumor diagnosis and treatment has shown substantial potentials in both preclinical and clinical studies. However, in preclinical settings, tumor-bearing mice exhibit relatively low absolute FAP expression levels, leading to challenges in acquiring high-quality PET images using radiolabeled FAP ligands (FAPIs) with low molar activity, because of which a saturation effect in imaging is prone to happen. Moreover, how exactly the molar dose of FAPI administered to a mouse influences the targeted PET imaging and radiotherapy remains unclear now.

Clinical Value of Abnormal Prothrombin and Carbohydrate Antigen 125 in the Diagnosis of Patients With Gallbladder Cancer.

Objective: This study was aimed at ascertaining the application value of abnormal prothrombin (PIVKA-II) and carbohydrate antigen 125 (CA125) in gallbladder cancer (GBC) diagnosis.

Methods: A total of 70 GBC patients, 70 patients with benign gallbladder diseases (gallbladder stones and gallbladder polyps), and 70 normal health examination people were selected as the malignant, benign, and normal groups, respectively. The differences in serum levels and positive rates of PIVKA-II and CA125 were compared.

Clinical value of microRNA-130a as a marker of acute liver failure and its involvement in disease development.

Objective: This study was to investigate the clinical value of microRNA (miR)-130a in acute liver failure (ALF).

Methods: ALF patients (n = 120, ALF group) and 106 healthy subjects (control group) were enrolled. Serum was collected to detect alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) by automatic biochemical analyzer, and miR-130a by real-time fluorescence quantitative PCR.

Chemical proteomics accelerates the target discovery of natural products.

More than half of the global novel drugs are directly or indirectly derived from natural products (NPs) because of their better selectivity towards proteins. Traditional medicines perform multiple bioactivities through various NPs binding to drug targets, which highlights the opportunities of target discovery for drug development. However, detecting the binding relationship between NPs and targets remains challenging.

Deciphering the causal association and underlying transcriptional mechanisms between telomere length and abdominal aortic aneurysm.

Background: The purpose of this study is to investigate the causal effect and potential mechanisms between telomere length and abdominal aortic aneurysm (AAA).

Methods: Summary statistics of telomere length and AAA were derived from IEU open genome-wide association studies and FinnGen R9, respectively. Bi-directional Mendelian randomization (MR) analysis was conducted to reveal the causal relationship between AAA and telomere length.

Peroxisome proliferator-activated receptors regulate the progression and treatment of gastrointestinal cancers.

Peroxisome proliferator-activated receptors (PPARs) are essential nuclear hormone receptors regulating metabolic processes, and they participate in the initiation and progression processes of tumors. Gastrointestinal (GI) cancer is a prevalent malignancy worldwide that originates from the tissues of the gastrointestinal tract and is characterized by severe symptoms and poor prognosis. Numerous published studies have investigated the critical role of PPARs in esophageal, gastric, and colorectal cancers.

m6A hypomethylation of DNMT3B regulated by ALKBH5 promotes intervertebral disc degeneration via E4F1 deficiency.

Background: The intervertebral disc (IVD) degeneration is the leading cause of low back pain, which accounts for a main cause of disability. N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic messenger RNAs and is involved in various diseases and cellular processes by modulating mRNA fate. However, the critical role of m6A regulation in IVD degeneration remains unclear.

WTAP-mediated mA modification of lncRNA NORAD promotes intervertebral disc degeneration.

N6-methyladenosine (mA) is the most prevalent RNA modification at the posttranscriptional level and involved in various diseases and cellular processes. However, the underlying mechanism of mA regulation in intervertebral disc degeneration (IVDD) remains elusive. Here, we show that methylation of the lncRNA NORAD significantly increases in senescent nucleus pulposus cells (NPCs) by mA sequencing.

Regulatory B cells improve ventricular remodeling after myocardial infarction by modulating monocyte migration.

Overactivated inflammatory responses contribute to adverse ventricular remodeling after myocardial infarction (MI). Regulatory B cells (Bregs) are a newly discovered subset of B cells with immunomodulatory roles in many immune and inflammation-related diseases. Our study aims to determine whether the expansion of Bregs exerts a beneficial effect on ventricular remodeling and explore the mechanisms involved.

Upregulation of PREX2 promotes the proliferation and migration of hepatocellular carcinoma cells via PTEN-AKT signaling.

Phosphatidylinositol-3,4,5-trisphosphate Rac exchanger 2 (PREX2), a regulator of the small guanosine triphosphatase Rac, demonstrates an inhibitory effect on the activity of phosphatase and tensin homolog (PTEN). Previously, PREX2 was implicated in the regulation of cell invasion in hepatocellular carcinoma (HCC). However, the exact role of PREX2 in the regulation of HCC cell proliferation and migration, as well as the underlying mechanisms, remains unclear.

Expression and function of microRNA-27b in hepatocellular carcinoma.

It has been reported that microRNAs (miRs) have key roles in tumorigenesis via inhibition of their target genes. Dysregulation of miR‑27b has been detected in numerous types of human cancer, including hepatocellular carcinoma (HCC); however, the detailed role of miR‑27b in HCC has yet to be elucidated. Reverse transcription‑quantitative polymerase chain reaction and western blotting were performed to examine the mRNA and protein expression levels.

MITF and PAX3 Play Distinct Roles in Melanoma Cell Migration; Outline of a "Genetic Switch" Theory Involving MITF and PAX3 in Proliferative and Invasive Phenotypes of Melanoma.

Melanoma is a very aggressive neoplasm with a propensity to undergo progression and invasion early in its evolution. The molecular pathways underpinning invasion in melanoma are now just beginning to be elucidated, but a clear understanding of the transition from non-invasive to invasive melanoma cells remains elusive. Microphthalmia-associated transcription factor (MITF), is thought to be a central player in melanoma biology, and it controls many aspects of the phenotypic expression of the melanocytic lineage.

PAX3 knockdown in metastatic melanoma cell lines does not reduce MITF expression.

PAX3 and MITF are important transcriptional activators in the melanocyte lineage and PAX3 is thought to control MITF expression during normal melanocyte differentiation. However, it is not clear whether this is still true in melanoma and whether the effects of knockdown of PAX3 on the inhibition of melanoma growth or survival are by its regulation of MITF. By western blot and quantitative real-time reverse transcription-PCR, we investigated the relationship between PAX3 and MITF expression in 27 metastatic melanoma and one immortalized melanocyte cell lines.

A gene expression signature of invasive potential in metastatic melanoma cells.

Background: We are investigating the molecular basis of melanoma by defining genomic characteristics that correlate with tumour phenotype in a novel panel of metastatic melanoma cell lines. The aim of this study is to identify new prognostic markers and therapeutic targets that might aid clinical cancer diagnosis and management.

Principal Findings: Global transcript profiling identified a signature featuring decreased expression of developmental and lineage specification genes including MITF, EDNRB, DCT, and TYR, and increased expression of genes involved in interaction with the extracellular environment, such as PLAUR, VCAN, and HIF1a.

PAX3 is expressed in the stromal compartment of the developing kidney and in Wilms tumors with myogenic phenotype.

Wilms tumor (WT) is the most frequent renal neoplasm of childhood; a myogenic component is observed in 5% to 10% of tumors. We demonstrate for the first time that myogenic WTs are associated with expression of PAX3, a transcription factor known to specify myoblast cell fate during muscle development. In a panel of 20 WTs, PAX3 was identified in 13 of 13 tumor samples with myogenic histopathology but was absent in 7 of 7 tumors lacking a myogenic component.

A PANorama of PAX genes in cancer and development.

Populations of self-renewing cells that arise during normal embryonic development harbour the potential for rapid proliferation, migration or transdifferentiation and, therefore, tumour generation. So, control mechanisms are essential to prevent rapidly expanding populations from malignant growth. Transcription factors have crucial roles in ensuring establishment of such regulation, with the Pax gene family prominent amongst these.

Transfection of melanoma cells with antisense PAX3 oligonucleotides additively complements cisplatin-induced cytotoxicity.

Advanced melanoma is difficult to treat, in part because of greater resistance to therapy compared with other cancer types. The mechanisms underlying this resistance are not well-understood. One factor that is reported to be involved in melanoma cell survival is PAX3, a transcription factor normally expressed during embryonic development, and which is critically required for development of neural crest-derivatives, including skin melanocytes.

WT1 is a modifier of the Pax2 mutant phenotype: cooperation and interaction between WT1 and Pax2.

Metanephric kidney development requires an inductive interaction between the ureteric bud and progenitor mesenchyme, where the early expression of two genes, Wilms' tumour 1 (WT1) and paired box 2 (Pax2), establishes critical but unknown developmental pathways. Indeed, transgenic mice with deregulated overexpression of Pax2 exhibit structural kidney defects and impaired renal function, as do mice harboring targeted disruptions and/or spontaneous mutations of either the Pax2 or WT1 genes. WT1 and Pax2 are thought to regulate each other's expression during renal development.

PAX genes in development and disease: the role of PAX2 in urogenital tract development.

PAX genes play an important role in fetal development. Moreover, heterozygous mutations in several PAX genes cause human disease. Here we review the role of PAX2 in kidney development, focusing on the morphological effects of PAX2 mutations.