A comprehensive pan-cancer analysis revealing the role of ITPRIPL1 as a prognostic and immunological biomarker.

Inositol 1,4,5-Trisphosphate Receptor-Interacting Protein-Like 1 (ITPRIPL1), a single-pass type I membrane protein located in the membrane, functions as an inhibitory ligand of CD3ε. Recent studies have shown that its expression suppresses T cells activation and promote tumor immune evasion. Despite increasing evidence suggesting that ITPRIPL1 plays a significant role in tumor growth, no systematic pan-cancer analysis of ITPRIPL1 has been conducted to date.

Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia.

The advent of tyrosine kinase inhibitors (TKI) targeting BCR-ABL has drastically changed the treatment approach of chronic myeloid leukemia (CML), greatly prolonged the life of CML patients, and improved their prognosis. However, TKI resistance is still a major problem with CML patients, reducing the efficacy of treatment and their quality of life. TKI resistance is mainly divided into BCR-ABL-dependent and BCR-ABL-independent resistance.

Development and evaluation of a human CD47/HER2 bispecific antibody for Trastuzumab-resistant breast cancer immunotherapy.

The treatment for trastuzumab-resistant breast cancer (BC) remains a challenge in clinical settings. It was known that CD47 is preferentially upregulated in HER2 BC cells, which is correlated with drug resistance to trastuzumab. Here, we developed a novel anti-CD47/HER2 bispecific antibody (BsAb) against trastuzumab-resistant BC, named IMM2902.

Identification of rare variants in PTCH2 associated with non-syndromic orofacial clefts.

Orofacial clefts (OFCs) represent the most prevalent congenital craniofacial anomalies, significantly impacting patients' appearance, oral function, and psychological well-being. Among these, non-syndromic OFCs (NSOFCs) are the most predominant type, with the etiology attributed to a combination of genetic and environmental factors. Rare variants of key genes involved in craniofacial development-related signaling pathway are crucial in the occurrence of NSOFCs, and our recent studies have identified PTCH1, a receptor-coding gene in the Hedgehog signaling pathway, as a causative gene for NSOFCs.

CoREST1 in primary sensory neurons regulates neuropathic pain in male mice.

Aims: Epigenetic regulation is implicated in the neurogenesis of neuropathic pain. The repressor element 1 (RE1) silencing transcription factor (REST) corepressor (CoREST) proteins function as corepressors in the REST complex and/or LSD1 epigenetic complex. In the current study, we aimed to find the expression profile of CoREST1 in the dorsal root ganglion (DRG) and investigate whether it plays a role in neuropathic pain.

Chimeric antigen receptor-immune cells against solid tumors: Structures, mechanisms, recent advances, and future developments.

The advent of chimeric antigen receptor (CAR)-T cell immunotherapies has led to breakthroughs in the treatment of hematological malignancies. However, their success in treating solid tumors has been limited. CAR-natural killer (NK) cells have several advantages over CAR-T cells because NK cells can be made from pre-existing cell lines or allogeneic NK cells with a mismatched major histocompatibility complex (MHC), which means they are more likely to become an "off-the-shelf" product.

Contributions of bone marrow monocytes/macrophages in myeloproliferative neoplasms with JAK2 mutation.

The classic BCR-ABL1-negative myeloproliferative neoplasm (MPN) is a highly heterogeneous hematologic tumor that includes three subtypes, namely polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). Despite having the same JAK2 mutation, the clinical manifestations of these three subtypes of MPN differ significantly, which suggests that the bone marrow (BM) immune microenvironment may also play an important role. In recent years, several studies have shown that peripheral blood monocytes play an important role in promoting MPN.

Identification of potential resistance mechanisms and therapeutic targets for the relapse of BCMA CAR-T therapy in relapsed/refractory multiple myeloma through single-cell sequencing.

Background: BCMA CAR-T is highly effective for relapsed/refractory multiple myeloma(R/R-MM) and significantly improves the survival of patients. However, the short remission time and high relapse rate of MM patients treated with BCMA CAR-T remain bottlenecks that limit long-term survival. The immune microenvironment of the bone marrow (BM) in R/R-MM may be responsible for this.

Identification of rare loss-of-function variants in FAM3B associated with non-syndromic orofacial clefts.

Orofacial clefts (OFCs) are the most common congenital craniofacial disorders and cause serious problems with the appearance, orofacial function and mental health of the patients. The fibroblast growth factor (FGF) signaling pathway is critical for several aspects of craniofacial development and loss-of-function mutations of coding genes for multiple FGFs and FGFRs can lead to OFCs. We recently characterized FAM3B as a novel ligand of FGF signaling, which, through binding to FGFRs and activating downstream ERK, regulates craniofacial development in Xenopus.

Targeting macrophages: a novel treatment strategy in solid tumors.

In the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are the most abundant immune cells, which act as a key regulator in tumorigenesis and progression. Increasing evidence have demonstrated that the TME alters the nature of macrophages to maintain dynamic tissue homeostasis, allowing TAMs to acquire the ability to stimulate angiogenesis, promote tumor metastasis and recurrence, and suppress anti-tumor immune responses. Furthermore, tumors with high TAM infiltration have poor prognoses and are resistant to treatment.

Nerve injury-induced upregulation of apolipoprotein E in dorsal root ganglion participates in neuropathic pain in male mice.

Apolipoprotein E (ApoE) is an apolipoprotein involved in lipid metabolism and is primarily responsible for lipid transport and cholesterol homeostasis in the central nervous system (CNS). The aim of this study is to explore the role of ApoE in the pathological development of neuropathic pain. First, we examined the location of ApoE in the dorsal root ganglion (DRG) and spinal cord in male mice using immunohistochemistry, and found that ApoE was predominantly expressed in DRG satellite glial cells (SGCs) and macrophages and spinal cord astrocytes.

A392V and R945X mutations cause orofacial clefts via impairing PTCH1 function.

The Hedgehog (HH) signaling plays key roles in embryogenesis and organogenesis, and its dysfunction causes a variety of human birth defects. Orofacial cleft (OFC) is one of the most common congenital craniofacial defects, and its etiology is closely related to mutations in multiple components in the HH pathway, including the PTCH1 receptor. A quantity of PTCH1 variants have been associated with OFC, but the pathogenicity and underlying mechanism of these variants have not been functionally validated.

Lysine-specific demethylase 1 in primary sensory neurons participates in chronic compression of dorsal root ganglion-induced neuropathic pain.

Low back and radicular pain syndromes, usually caused by local inflammation and irritation to the nerve root and dorsal root ganglion (DRG), are common throughout medical practice, but sufficient pain relief is scarce. In this study, we employed a chronic compression of DRG (CCD)-induced radicular pain model in rats to explore whether lysine-specific demethylase 1 (LSD1), a histone demethylase and transcriptional co-repressor, is involved in the pathological process of radicular pain. We found that LSD1 was expressed in various-sized DRG neurons by immunohistochemistry.

Matrix metalloproteinase 1 is a poor prognostic biomarker for patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains an incurable malignancy despite the treatment methods being continually updated. Matrix metalloproteinases (MMPs) promote the progression of HCC; however, no consensus exists on which MMP plays the predominant role in HCCs. In the present study, we analyzed differentially expressed genes in HCCs, especially MMPs, compared with adjacent tissues using the Cancer Genome Atlas database.

Identification of macrophage correlated biomarkers to predict the prognosis in patients with intrahepatic cholangiocarcinoma.

Background: It has been shown that tumor-associated immune cells, particularly macrophages, play a fundamental role in the development and treatment response of intrahepatic cholangiocarcinoma (ICC). However, little is known about macrophages at the single cellular level of ICC patients.

Methods: ScRNA-seq from Zhang et al.

SIRPα and PD1 expression on tumor-associated macrophage predict prognosis of intrahepatic cholangiocarcinoma.

Background: The phagocytosis checkpoints of CD47/SIRPα, PD1/PDL1, CD24/SIGLEC10, and MHC/LILRB1 have shown inhibited phagocytosis of macrophages in distinct tumors. However, phagocytosis checkpoints and their therapeutic significance remain largely unknown in intrahepatic cholangiocarcinoma (ICC) patients.

Methods: We analyzed sequencing data from the Cancer Genome Atlas (TCGA) and identified differently expressed genes between tumors and para-tumors.

Polymorphisms in lncRNA and susceptibility to breast cancer in Chinese population.

Background: Published studies based on pharmacokinetics have explored the relationship between the lncRNA and the prognosis of breast cancer (BC) resistance and recurrence. However, the underlying association of SNPs with BC development remains unclear.

Methods: Combining bioinformatics and databases, SNPs (Single Nucleotide Polymorphisms) in the gene were screened, and SNPs in the lncRNA were selected for genotyping among 504 Chinese Han patients and 505 healthy controls, which were frequency-matched for age (±2 years).

5-HT Receptor Is Involved in Electroacupuncture Inhibition of Chronic Pain in the Spinal Cord.

Knee osteoarthritis (KOA) is a common and disabling condition characterized by attacks of pain around the joints, and it is a typical disease that develops chronic pain. Previous studies have proved that 5-HT, 5-HT, and 5-HT receptors in the spinal cord are involved in electroacupuncture (EA) analgesia. The 5-HT receptor plays antinociceptive role in the spinal cord.

The cytokine FAM3B/PANDER is an FGFR ligand that promotes posterior development in .

Fibroblast growth factor (FGF)/extracellular signal-regulated kinase (ERK) signaling plays a crucial role in anterior-posterior (A-P) axial patterning of vertebrate embryos by promoting posterior development. In our screens for novel developmental regulators in embryos, we identified Fam3b as a secreted factor regulated in ectodermal explants. Family with sequence similarity 3 member B (FAM3B)/PANDER (pancreatic-derived factor) is a cytokine involved in glucose metabolism, type 2 diabetes, and cancer in mammals.

The biology of combination immunotherapy in recurrent metastatic head and neck cancer.

Preclinical data suggest that head and neck cancer is an intrinsically immunosuppressive disease with abnormal inflammatory components in the tumor microenvironment. The development of immune checkpoint inhibitors, which are monoclonal antibodies capable of inhibiting immune suppressive signals to prime anticancer immunity, has revolutionized the therapeutic landscape in recurrent/metastatic head and neck cancer. However, patients with head and neck cancer present primary resistance to immunotherapy.

Upregulation of LINC01426 promotes the progression and stemness in lung adenocarcinoma by enhancing the level of SHH protein to activate the hedgehog pathway.

Long noncoding RNAs (lncRNAs) play crucial roles in regulating a variety of biological processes in lung adenocarcinoma (LUAD). In our study, we mainly explored the functional roles of a novel lncRNA long intergenic non-protein coding RNA 1426 (LINC01426) in LUAD. We applied bioinformatics analysis to find the expression of LINC01426 was upregulated in LUAD tissue.

Regulation of PD-L1 expression in the tumor microenvironment.

Programmed death-ligand 1 (PD-L1) on cancer cells engages with programmed cell death-1 (PD-1) on immune cells, contributing to cancer immune escape. For multiple cancer types, the PD-1/PD-L1 axis is the major speed-limiting step of the anti-cancer immune response. In this context, blocking PD-1/PD-L1 could restore T cells from exhausted status and eradicate cancer cells.

Electro-acupuncture Suppresses AXL Expression in Dorsal Root Ganglion Neurons and Enhances Analgesic Effect of AXL Inhibitor in Spinal Nerve Ligation Induced-Neuropathic Pain Rats.

Electro-acupuncture (EA) has been used for clinic analgesia for many years. However, its mechanisms are not fully understood. We recently reported that AXL, a tyrosine kinase receptor, contributes to the peripheral mechanism of neuropathic pain.