Structural basis of tethered agonism and G protein coupling of protease-activated receptors.

Protease-activated receptors (PARs) are a unique group within the G protein-coupled receptor superfamily, orchestrating cellular responses to extracellular proteases via enzymatic cleavage, which triggers intracellular signaling pathways. Protease-activated receptor 1 (PAR1) is a key member of this family and is recognized as a critical pharmacological target for managing thrombotic disorders. In this study, we present cryo-electron microscopy structures of PAR1 in its activated state, induced by its natural tethered agonist (TA), in complex with two distinct downstream proteins, the G and G heterotrimers, respectively.

Soluble Periostin is a potential surveillance biomarker for early and long-term response to chemotherapy in advanced breast cancer.

Background: Noninvasive biomarkers for the assessment of response to chemotherapy in advanced breast cancer (BCa) are essential for optimized therapeutic decision-making. We evaluated the potential of soluble Periostin (POSTN) in circulation as a novel biomarker for chemotherapy efficacy monitoring.

Methods: Two hundred and thirty-one patients with different stages of BCa were included.

Soluble POSTN is a novel biomarker complementing CA153 and CEA for breast cancer diagnosis and metastasis prediction.

Background: Breast cancer (BCa) is the leading cause of cancer deaths among women. Reliable biomarkers for early diagnosis and metastasis prediction are essential to improve the prognosis of BCa. This study aimed to evaluate serum periostin (POSTN) as a novel biomarker complementing CA153 (carbohydrate antigen 153) and CEA (carcinoembryonic antigen) for BCa diagnosis and metastasis prediction.

High Histone Deacetylase 2/3 Expression in Non-Functioning Pituitary Tumors.

Epigenetic modification of chromatin is involved in non-malignant pituitary neoplasia by causing abnormal expression of tumor suppressors and oncogenes. These changes are potentially reversible, suggesting the possibility of targeting tumor cells by restoring the expression of epigenetically silenced tumor suppressors. The role of the histone deacetylase (HDAC) family in pituitary tumorigenesis is not known.

Sprouting Angiogenesis in Human Pituitary Adenomas.

Introduction: Angiogenesis in pituitary tumors is not fully understood, and a better understanding could help inform new pharmacologic therapies, particularly for aggressive pituitary tumors.

Materials And Methods: 219 human pituitary tumors and 12 normal pituitary glands were studied. Angiogenic genes were quantified by an angiogenesis qPCR array and a TaqMan probe-based absolute qPCR.

Promoter methylation-mediated repression of UNC5 receptors and the associated clinical significance in human colorectal cancer.

Background: Deregulated methylation of tumor suppressor genes is a hallmark event in colorectal cancer (CRC) carcinogenesis. UNC5 receptors, down-regulated in various human malignancies due to epigenetic alterations, have been proposed as putative tumor suppressor genes. In this study, we focused on the methylation-mediated inhibition of UNC5 receptors and the associated clinical significance in CRC.

The Upregulation of Molecules Related to Tumor Immune Escape in Human Pituitary Adenomas.

Human pituitary adenomas are one of the most common intracranial neoplasms. Although most of these tumors are benign and can be treated medically or by transsphenoidal surgery, a subset of these tumors are fast-growing, aggressive, recur, and remain a therapeutic dilemma. Because antibodies against immune checkpoint receptors PD-1 and CLTA-4 are now routinely used for cancer treatment, we quantified the expression of mRNA coding for PD-1, CLTA-4, and their ligands, PD-L1, PD-L2, CD80, and CD86 in human pituitary adenomas and normal pituitary glands, with the ultimate goal of exploiting immune checkpoint therapy in aggressive pituitary adenomas.

A TTP-incorporated scoring model for predicting mortality of solid tumor patients with bloodstream infection caused by Escherichia coli.

Background: Few mortality-scoring models are available for solid tumor patients who are predisposed to develop Escherichia coli-caused bloodstream infection (ECBSI). We aimed to develop a mortality-scoring model by using information from blood culture time to positivity (TTP) and other clinical variables.

Methods: A cohort of solid tumor patients who were admitted to hospital with ECBSI and received empirical antimicrobial therapy was enrolled.

A cross-nearest neighbor/Monte Carlo algorithm for single-molecule localization microscopy defines interactions between p53, Mdm2, and MEG3.

The functions of long noncoding (lnc)RNAs, such as MEG3, are defined by their interactions with other RNAs and proteins. These interactions, in turn, are shaped by their subcellular localization and temporal context. Therefore, it is important to be able to analyze the relationships of lncRNAs while preserving cellular architecture.

TGFβ regulates NK1R-Tr to affect the proliferation and apoptosis of breast cancer cells.

Objectives: TGFβ promotes cancer aggressiveness in advanced stages. NK1R-Tr expression in advanced breast cancer has a pro-carcinogenic effect. In this study, we aimed to investigate the effect of the association of TGFβ with NK1R-Tr expression on the proliferation and apoptosis of breast cancer cells.

Preparation and evaluation of PEGylated asiatic acid nanostructured lipid carriers on anti-fibrosis effects.

Liver fibrosis is a major pathological feature of chronic liver diseases, and effective therapies are limited at present. Asiatic acid (AA) is a triterpenoid isolated from , which exhibits efficient anti-inflammatory and anti-oxidative activities. However, AA shows very low plasma levels after oral administration.

miR-206 Promotes Cancer Progression by Targeting Full-Length Neurokinin-1 Receptor in Breast Cancer.

Substance P plays a pivotal role in human cancer development and progression by binding to its receptor, neurokinin-1. Neurokinin-1 has 2 isoforms: full-length neurokinin-1 and truncated neurokinin-1, the latter lacking the cytoplasmic terminal 96-amino acid residues of the full-length protein. We have identified 3 candidate miR-206 target sites within the 3'-untranslated region of the full-length neurokinin-1 gene from bioinformatics database searches.

Meg3-DMR, not the Meg3 gene, regulates imprinting of the Dlk1-Dio3 locus.

The imprinted delta like 1 homolog (DLK1) - thyroxine deiodinase type III (DIO3) locus regulates development and growth. Its imprinting regulation involves two differentially methylated regions (DMRs), intergenic-DMR (IG-DMR) and maternally expressed gene 3-DMR (Meg3-DMR). In mice, a maternal deletion of the IG-DMR leads to LOI in the locus, proving that the IG-DMR is a cis-acting imprinting control region of the locus.

Identification of a novel HLA-B*15 allele, HLA-B*15:504, in a Chinese individual.

The new allele HLA-B*15:504 showed one nucleotide difference compared to B*15:18:01 at position 142 (T > G).

A novel HLA-A*02 allele, A*02:828, identified by next-generation sequencing in a Chinese individual.

HLA-A*02:828 differs from A*02:01:01:01 by a single non-synonymous mutation in exon 2.

Identification of two novel HLA class II alleles, HLA-DQB1*02:139 and HLA-DQB1*02:140, in northern Chinese individuals.

Two novel HLA-DQB1 alleles, HLA-DQB1*02:139 and HLA-DQB1*02:140, characterized using a sequence-based typing in northern Chinese individuals.

The long non-coding RNA Meg3 is dispensable for hematopoietic stem cells.

The long non-coding RNA (lncRNA) Maternally Expressed Gene 3 (Meg3) is encoded within the imprinted Dlk1-Meg3 gene locus and is only maternally expressed. Meg3 has been shown to play an important role in the regulation of cellular proliferation and functions as a tumor suppressor in numerous tissues. Meg3 is highly expressed in mouse adult hematopoietic stem cells (HSCs) and strongly down-regulated in early progenitors.

UNC5D, suppressed by promoter hypermethylation, inhibits cell metastasis by activating death-associated protein kinase 1 in prostate cancer.

Prostate cancer (PCa) death primarily occurs due to metastasis of the cells, but little is known about the underlying molecular mechanisms. This study aimed to evaluate the expression of UNC5D, a newly identified tumor suppressor gene, analyze its epigenetic alterations, and elucidate its functional relevance to PCa metastasis. Meta-analysis of publicly available microarray datasets revealed that UNC5D expression was frequently downregulated in PCa tissues and inversely associated with PCa metastasis.

MicroRNA-22 inhibits proliferation, invasion and metastasis of breast cancer cells through targeting truncated neurokinin-1 receptor and ERα.

Heading Aims: This topic aims to clarify whether miR-22 directly targets and downregulates the expression of ERα and NK1R-Tr to inhibit the malignant behaviors of breast cancer cells.

Materials And Methods: RT-PCR and Western Blotting were used to detect the expression profile of miR-22, NK1R-Tr and ERα. Luciferase reporter assay and CHIP experiment were conducted to investigate the regulation network between miR-22, NK1R-Tr and ERα.

MiR-34b/c-5p and the neurokinin-1 receptor regulate breast cancer cell proliferation and apoptosis.

Objectives: MiR-34 is a tumour suppressor in breast cancer. Neurokinin-1 receptor (NK1R), which is the predicted target of the miR-34 family, is overexpressed in many cancers. This study investigated the correlation and clinical significance of miR-34 and NK1R in breast cancer.

Identification of Serum Periostin as a Potential Diagnostic and Prognostic Marker for Colorectal Cancer.

Background: Periostin (POSTN) plays an important role in numerous cancers, especially in gastrointestinal malignancy. The objective of this study was to investigate the diagnostic and prognostic role of serum POSTN in colorectal cancer (CRC).

Methods: Serum periostin, together with CEA, CA19.

Periostin and CA242 as potential diagnostic serum biomarkers complementing CA19.9 in detecting pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with few biomarkers to guide treatment options. Carbohydrate antigen 19.9 (CA19.

Lapatinib Inhibits Breast Cancer Cell Proliferation by Influencing PKM2 Expression.

Pyruvate kinase type M2, which is expressed in multiple tumor cell types and plays a key role in aerobic glycolysis, also has nonglycolytic functions and can regulate transcription and cell proliferation. The results of this study show that epidermal growth factor receptor activation induces pyruvate kinase type M2 nuclear translocation. To further determine the relationship between pyruvate kinase type M2 and epidermal growth factor receptor, we analyzed pathological data from mammary glands and performed epidermal growth factor receptor/human epidermal growth factor receptor 2 knockdown to reveal that pyruvate kinase type M2 is associated with epidermal growth factor receptor and human epidermal growth factor receptor 2.

Enzyme Kinetic Assay to Measure the Activity of Tumor M2 Pyruvate Kinase in Breast Cancer Patients.

Background: M2 type Pyruvate kinase (PKM2) is the key rate-limiting enzyme of glycolysis, and it mainly exists as a dimer in tumor cells. This study aims to establish an enzyme kinetic assay for serum tumor M2 pyruvate kinase (TuM2-PK), and to evaluate its diagnostic value in breast cancer.

Methods: The catalytic kinetics of Pyruvate Kinase (PK) was examined.

Evaluating EFEMP1 in Cerebrospinal Fluid and Serum as a Potential Diagnosis Biomarker for Meningiomas.

Background: The aim of this study was to determine the cerebrospinal fluid (CSF) and serum levels of EGF containing fibulin-like extracellular matrix protein 1 (EFEMP1) in the patients with meningiomas and explore its potential as a biomarker.

Methods: Forty-five patients with meningioma, 11 of whom underwent meningioma resection, as well as 30 healthy controls were enrolled in this study. CSF and blood samples were collected preoperatively and postoperatively.